Publications by authors named "Jeff S Volek"

270 Publications

Acute Effects of High-intensity Resistance Exercise on Cognitive Function.

J Sports Sci Med 2021 Sep 3;20(3):391-397. Epub 2021 May 3.

Department of Psychology, The Ohio State University, Columbus, OH, USA.

The purpose of the present study was to examine the influence of an acute bout of high-intensity resistance exercise on measures of cognitive function. Ten men (Mean ± SD: age = 24.4 ± 3.2 yrs; body mass = 85.7 ± 11.8 kg; height = 1.78 ± 0.08 m; 1 repetition maximum (1RM) = 139.0 ± 24.1 kg) gave informed consent and performed a high-intensity 6 sets of 10 repetitions of barbell back squat exercise at 80% 1RM with 2 minutes rest between sets. The Automated Neuropsychological Assessment Metrics (ANAM) was completed to assess various cognitive domains during the familiarization period, immediately before, and immediately after the high-intensity resistance exercise bout. The repeated measures ANOVAs for throughput scores (r·m) demonstrated significant mean differences for the Mathematical Processing task (MTH; < 0.001, η = 0.625) where pairwise comparisons demonstrated that the post-fatigue throughput (32.0 ± 8.8 r·m) was significantly greater than the pre-fatigue (23.8 ± 7.4 r·m, = 0.003, = 1.01) and the familiarization throughput (26.4 ± 5.3 r·m, = 0.024, = 0.77). The Coded Substitution-Delay task also demonstrated significant mean differences (CDD; = 0.027, η = 0.394) with pairwise comparisons demonstrating that the post-fatigue throughput (49.3 ± 14.4 r·m) was significantly less than the pre-fatigue throughput (63.2 ± 9.6 r·m, = 0.011, = 1.14). The repeated measures ANOVAs for reaction time (ms) demonstrated significant mean differences for MTH ( < 0.001, η = 0.624) where pairwise comparisons demonstrated that the post-fatigue reaction time (1885.2 ± 582.8 ms) was significantly less than the pre-fatigue (2518.2 ± 884.8 ms, = 0.005, = 0.85) and familiarization (2253.7 ± 567.6 ms, = 0.009, = 0.64) reaction times. The Go/No-Go task demonstrated significant mean differences (GNG; = 0.031, η = 0.320) with pairwise comparisons demonstrating that the post-fatigue (285.9 ± 16.3 ms) was significantly less than the pre-fatigue (298.5 ± 12.1 ms, = 0.006, = 0.88) reaction times. High-intensity resistance exercise may elicit domain-specific influences on cognitive function, characterized by the facilitation of simple cognitive tasks and impairments of complex cognitive tasks.
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http://dx.doi.org/10.52082/jssm.2021.391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256515PMC
September 2021

Treating Alpelisib-Induced Hyperglycemia with Very Low Carbohydrate Diets and Sodium-Glucose Co-Transporter 2 Inhibitors: A Case Series.

Integr Cancer Ther 2021 Jan-Dec;20:15347354211032283

Weill Cornell Medicine, New York, NY, USA.

Alpelisib is a α-selective phosphatidylinositol 3-kinase (PI3K) inhibitor approved for treatment of postmenopausal women, and men, with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), PIK3CA-mutated, advanced breast cancer (ABC). Hyperglycemia is a common, on-target adverse effect that impairs treatment efficacy and increases the rate of treatment delays, dose reductions, and discontinuation. Currently, there are no clear guidelines on how to manage hyperglycemia due to alpelisib when metformin is not effective. In this case series, we review 3 subjects with ABC that developed hyperglycemia during alpelisib-fulvestrant therapy and were successfully managed with dietary and pharmacologic interventions. These cases provide anecdotal evidence to support the use of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and very low carbohydrate diets to minimize hyperglycemia during alpelisib therapy.
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http://dx.doi.org/10.1177/15347354211032283DOI Listing
July 2021

Effects of Palm Stearin versus Butter in the Context of Low-Carbohydrate/High-Fat and High-Carbohydrate/Low-Fat Diets on Circulating Lipids in a Controlled Feeding Study in Healthy Humans.

Nutrients 2021 Jun 5;13(6). Epub 2021 Jun 5.

Department of Human Sciences, The Ohio State University, 305 Annie & John Glenn Ave, Columbus, OH 43210, USA.

Background: Foods rich in saturated fatty acids (SFAs) have been discouraged by virtue of their cholesterol-raising potential, but this effect is modulated by the food source and background level of carbohydrate.

Objective: We aimed to compare the consumption of palm stearin (PS) versus butter on circulating cholesterol responses in the setting of both a low-carbohydrate/high-fat (LC/HF) and high-carbohydrate/low-fat (HC/LF) diet in healthy subjects. We also explored effects on plasma lipoprotein particle distribution and fatty acid composition.

Methods: We performed a randomized, controlled-feeding, cross-over study that compared a PS- versus a Butter-based diet in a group of normocholesterolemic, non-obese adults. A controlled canola oil-based 'Run-In' diet preceded the experimental PS and Butter diets. All diets were eucaloric, provided for 3-weeks, and had the same macronutrient distribution but varied in primary fat source (40% of the total fat). The same Run-In and cross-over experiments were done in two separate groups who self-selected to either a LC/HF ( = 12) or a HC/LF ( = 12) diet track. The primary outcomes were low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein (HDL)-C, triglycerides, and LDL particle distribution.

Results: Compared to PS, Butter resulted in higher LDL-C in both the LC/HF (13.4%, = 0.003) and HC/LF (10.8%, = 0.002) groups, which was primarily attributed to large LDL I and LDL IIa particles. There were no differences between PS and Butter in HDL-C, triglycerides, or small LDL particles. Oxidized LDL was lower after PS than Butter in LC/HF ( = 0.011), but not the HC/LF group.

Conclusions: These results demonstrate that Butter raises LDL-C relative to PS in healthy normocholesterolemic adults regardless of background variations in carbohydrate and fat, an effect primarily attributed to larger cholesterol-rich LDL particles.
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http://dx.doi.org/10.3390/nu13061944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226735PMC
June 2021

Hormonal stress responses of growth hormone and insulin-like growth factor-I in highly resistance trained women and men.

Growth Horm IGF Res 2021 Aug 6;59:101407. Epub 2021 Jun 6.

Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA.

The purpose of this study was to examine the responses of growth hormone (GH) and insulin-like growth factor-I (IGFI) to intense heavy resistance exercise in highly trained men and women to determine what sex-dependent responses may exist. Subjects were highly resistance trained men (N = 8, Mean ± SD; age, yrs., 21 ± 1, height, cm, 175.3 ± 6.7, body mass, kg, 87.0 ± 18.5, % body fat, 15.2 ± 5.4, squat X body mass, 2.1 ± 0.4; and women (N = 7; Mean ± SD, age, yrs. 24 ± 5, height, cm 164.6 ± 6.7, body mass, kg 76.4 ± 8.8, % body fat, 26.9 ± 5.3, squat X body mass, 1.7 ± 0.6). An acute resistance exercise test protocol (ARET) consisted of 6 sets of 10 repetitions at 80% of the 1 RM with 2 min rest between sets was used as the stressor. Blood samples were obtained pre-exercise, after 3 sets, and then immediately after exercise (IP), 5, 15, 30, and 70 min post-exercise for determination of blood lactate (HLa), and plasma glucose, insulin, cortisol, and GH. Determination of plasma concentrations of IGFI, IGF binding proteins 1, 2, and 3 along with molecular weight isoform factions were determined at pre, IP and 70 min. GH significantly (P ≤ 0.05) increased at all time points with resting concentrations significantly higher in women. Significant increases were observed for HLa, glucose, insulin, and cortisol with exercise and into recovery with no sex-dependent observations. Women showed IGF-I values that were higher than men at all times points with both seeing exercise increases. IGFBP-1 and 2 showed increase with exercise with no sex-dependent differences. IGFBP-3 concentrations were higher in women at all-time points with no exercise induced changes. Both women and men saw an exercise induced increase with significantly higher values in GH in only the mid-range (30-60 kD) isoform.  Only women saw an exercise induced increase with significantly higher values for IGF fractions only in the mid-range (30-60 kD) isoform, which were significantly greater than the men at the IP and 70 min post-exercise time points. In conclusion, the salient findings of this investigation were that in highly resistance trained men and women, sexual dimorphisms exist but appear different from our prior work in untrained men and women and appear to support a sexual dimorphism related to compensatory aspects in women for anabolic mediating mechanisms in cellular interactions.
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http://dx.doi.org/10.1016/j.ghir.2021.101407DOI Listing
August 2021

The Effects of a 6-Week Controlled, Hypocaloric Ketogenic Diet, With and Without Exogenous Ketone Salts, on Body Composition Responses.

Front Nutr 2021 24;8:618520. Epub 2021 Mar 24.

Department of Human Sciences, The Ohio State University, Columbus, OH, United States.

Ketogenic diets () that elevate beta-hydroxybutyrate () promote weight and fat loss. Exogenous ketones, such as ketone salts (), 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. To explore the effects of energy-matched, hypocaloric KD feeding (<50 g carbohydrates/day; 1.5 g/kg/day protein), with and without the inclusion of KS, on weight loss and body composition responses. 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; = 12) or placebo (KD + PL; = 13). A matched comparison group ( = 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. The KD induced nutritional ketosis (>1.0 mM capillary BHB) throughout the study ( < 0.001), with higher fasting concentrations observed in KD + KS than KD + PL for the first 2 weeks ( < 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 ( < 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 ( < 0.01) and trended higher in KD + PL compared to KD + KS ( = 0.076), whereas the nitrogen excretion during KD + KS was similar to LFD ( > 0.05). 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.
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http://dx.doi.org/10.3389/fnut.2021.618520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044842PMC
March 2021

Comparison of Ketogenic Diets with and without Ketone Salts versus a Low-Fat Diet: Liver Fat Responses in Overweight Adults.

Nutrients 2021 Mar 17;13(3). Epub 2021 Mar 17.

Department of Human Sciences, The Ohio State University, Columbus, OH 43201, USA.

Ketogenic diets (KDs) often contain high levels of saturated fat, which may increase liver fat, but the lower carbohydrate intake may have the opposite effect. Using a controlled feeding design, we compared liver fat responses to a hypocaloric KD with a placebo (PL) versus an energy-matched low-fat diet (LFD) in overweight adults. We also examined the added effect of a ketone supplement (KS). Overweight adults were randomized to a 6-week KD (KD + PL) or a KD with KS (KD + KS); an LFD group was recruited separately. All diets were estimated to provide 75% of energy expenditure. Weight loss was similar between groups ( > 0.05). Liver fat assessed by magnetic resonance imaging decreased after 6 week ( = 0.004) with no group differences ( > 0.05). A subset with nonalcoholic fatty liver disease (NAFLD) (liver fat > 5%, = 12) showed a greater reduction in liver fat, but no group differences. In KD participants with NAFLD, 92% of the variability in change in liver fat was explained by baseline liver fat ( < 0.001). A short-term hypocaloric KD high in saturated fat does not adversely impact liver health and is not impacted by exogenous ketones. Hypocaloric low-fat and KDs can both be used in the short-term to significantly reduce liver fat in individuals with NAFLD.
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http://dx.doi.org/10.3390/nu13030966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002465PMC
March 2021

Type 2 Diabetes Prevention Focused on Normalization of Glycemia: A Two-Year Pilot Study.

Nutrients 2021 Feb 26;13(3). Epub 2021 Feb 26.

Virta Health, San Francisco, CA 94105, USA.

The purpose of this study is to assess the effects of an alternative approach to type 2 diabetes prevention. Ninety-six patients with prediabetes (age 52 (10) years; 80% female; BMI 39.2 (7.1) kg/m) received a continuous remote care intervention focused on reducing hyperglycemia through carbohydrate restricted nutrition therapy for two years in a single arm, prospective, longitudinal pilot study. Two-year retention was 75% (72 of 96 participants). Fifty-one percent of participants (49 of 96) met carbohydrate restriction goals as assessed by blood beta-hydroxybutyrate concentrations for more than one-third of reported measurements. Estimated cumulative incidence of normoglycemia (HbA1c <5.7% without medication) and type 2 diabetes (HbA1c ≥6.5% or <6.5% with medication other than metformin) at two years were 52.3% and 3%, respectively. Prevalence of metabolic syndrome, class II or greater obesity, and suspected hepatic steatosis significantly decreased at two years. These results demonstrate the potential utility of an alternate approach to type 2 diabetes prevention, carbohydrate restricted nutrition therapy delivered through a continuous remote care model, for normalization of glycemia and improvement in related comorbidities.
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http://dx.doi.org/10.3390/nu13030749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996820PMC
February 2021

Differences in brain structure and theta burst stimulation-induced plasticity implicate the corticomotor system in loss of function after musculoskeletal injury.

J Neurophysiol 2021 04 17;125(4):1006-1021. Epub 2021 Feb 17.

Department of Human Sciences, The Ohio State University, Columbus, Ohio.

Traumatic musculoskeletal injury (MSI) may involve changes in corticomotor structure and function, but direct evidence is needed. To determine the corticomotor basis of MSI, we examined interactions among skeletomotor function, corticospinal excitability, corticomotor structure (cortical thickness and white matter microstructure), and intermittent theta burst stimulation (iTBS)-induced plasticity. Nine women with unilateral anterior cruciate ligament rupture (ACL) 3.2 ± 1.1 yr prior to the study and 11 matched controls (CON) completed an MRI session followed by an offline plasticity-probing protocol using a randomized, sham-controlled, double-blind, cross-over study design. iTBS was applied to the injured (ACL) or nondominant (CON) motor cortex leg representation (M1) with plasticity assessed based on changes in skeletomotor function and corticospinal excitability compared with sham iTBS. The results showed persistent loss of function in the injured quadriceps, compensatory adaptations in the uninjured quadriceps and both hamstrings, and injury-specific increases in corticospinal excitability. Injury was associated with lateralized reductions in paracentral lobule thickness, greater centrality of nonleg corticomotor regions, and increased primary somatosensory cortex leg area inefficiency and eccentricity. Individual responses to iTBS were consistent with the principles of homeostatic metaplasticity; corresponded to injury-related differences in skeletomotor function, corticospinal excitability, and corticomotor structure; and suggested that corticomotor adaptations involve both hemispheres. Moreover, iTBS normalized skeletomotor function and corticospinal excitability in ACL. The results of this investigation directly confirm corticomotor involvement in chronic loss of function after traumatic MSI, emphasize the sensitivity of the corticomotor system to skeletomotor events and behaviors, and raise the possibility that brain-targeted therapies could improve recovery. Traumatic musculoskeletal injuries may involve adaptive changes in the brain that contribute to loss of function. Our combination of neuroimaging and theta burst transcranial magnetic stimulation (iTBS) revealed distinct patterns of iTBS-induced plasticity that normalized differences in muscle and brain function evident years after unilateral knee ligament rupture. Individual responses to iTBS corresponded to injury-specific differences in brain structure and physiological activity, depended on skeletomotor deficit severity, and suggested that corticomotor adaptations involve both hemispheres.
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http://dx.doi.org/10.1152/jn.00689.2020DOI Listing
April 2021

Impact of a 2-year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabetes.

Cardiovasc Diabetol 2020 12 8;19(1):208. Epub 2020 Dec 8.

School of Medicine, University of California, San Francisco, CA, 94143, USA.

Background: We have previously reported that in patients with type 2 diabetes (T2D) consumption of a very low carbohydrate diet capable of inducing nutritional ketosis over 2 years (continuous care intervention, CCI) resulted in improved body weight, glycemic control, and multiple risk factors for cardiovascular disease (CVD) with the exception of an increase in low density lipoprotein cholesterol (LDL-C). In the present study, we report the impact of this intervention on markers of risk for atherosclerotic cardiovascular disease (CVD), with a focus on lipoprotein subfraction particle concentrations as well as carotid-artery intima-media thickness (CIMT).

Methods: Analyses were performed in patients with T2D who completed 2 years of this study (CCI; n = 194; usual care (UC): n = 68). Lipoprotein subfraction particle concentrations were measured by ion mobility at baseline, 1, and 2 years and CIMT was measured at baseline and 2 years. Principal component analysis (PCA) was used to assess changes in independent clusters of lipoprotein particles.

Results: At 2 years, CCI resulted in a 23% decrease of small LDL IIIb and a 29% increase of large LDL I with no change in total LDL particle concentration or ApoB. The change in proportion of smaller and larger LDL was reflected by reversal of the small LDL subclass phenotype B in a high proportion of CCI participants (48.1%) and a shift in the principal component (PC) representing the atherogenic lipoprotein phenotype characteristic of T2D from a major to a secondary component of the total variance. The increase in LDL-C in the CCI group was mainly attributed to larger cholesterol-enriched LDL particles. CIMT showed no change in either the CCI or UC group.

Conclusion: Consumption of a very low carbohydrate diet with nutritional ketosis for 2 years in patients with type 2 diabetes lowered levels of small LDL particles that are commonly increased in diabetic dyslipidemia and are a marker for heightened CVD risk. A corresponding increase in concentrations of larger LDL particles was responsible for higher levels of plasma LDL-C. The lack of increase in total LDL particles, ApoB, and in progression of CIMT, provide supporting evidence that this dietary intervention did not adversely affect risk of CVD.
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http://dx.doi.org/10.1186/s12933-020-01178-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724865PMC
December 2020

Body Composition in Elite Strongman Competitors.

J Strength Cond Res 2020 Dec;34(12):3326-3330

Division of Sports Medicine, Department of Orthopedics, Miller School of Medicine, University of Miami Sports Medicine Institute, Coral Gables, Florida.

Kraemer, WJ, Caldwell, LK, Post, EM, DuPont, WH, Martini, ER, Ratamess, NA, Szivak, TK, Shurley, JP, Beeler, MK, Volek, JS, Maresh, CM, Todd, JS, Walrod, BJ, Hyde, PN, Fairman, C, and Best, TM. Body composition in elite strongman competitors. J Strength Cond Res 34(12): 3326-3330, 2020-The purpose of this descriptive investigation was to characterize a group of elite strongman competitors to document the body composition of this unique population of strength athletes. Data were collected from eligible competitors as part of a health screening program conducted over 5 consecutive years. Imaging was acquired using dual-energy x-ray absorptiometry (DXA), providing total body measures of fat mass, lean mass, and bone mineral content (BMC). Year to year, testing groups showed a homogenous grouping of anthropometric, body composition, and bone density metrics. Composite averages were calculated to provide an anthropometric profile of the elite strongman competitor (N = 18; mean ± SD): age, 33.0 ± 5.2 years; body height, 187.4 ± 7.1 cm; body mass, 152.9 ± 19.3 kg; body mass index, 43.5 ± 4.8 kg·m; fat mass, 30.9 ± 11.1 kg; lean mass, 118.0 ± 11.7 kg, body fat, 18.7 ± 6.2%, total BMC, 5.23 ± 0.41 kg, and bone mineral density, 1.78 ± 0.14 g·cm. These data demonstrate that elite strongman competitors are among the largest human male athletes, and in some cases, they are at the extreme limits reported for body size and structure. Elite strongman competitors undergo a high degree of mechanical stress, providing further insight into the potent role of physical training in mediating structural remodeling even into adulthood. Such data provide a glimpse into a unique group of competitive athletes pushing the limits not only of human performance but also of human physiology.
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http://dx.doi.org/10.1519/JSC.0000000000003763DOI Listing
December 2020

Recovery using "float" from high intensity stress on growth hormone-like molecules in resistance trained men.

Growth Horm IGF Res 2020 12 25;55:101355. Epub 2020 Sep 25.

Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, United States of America.

Objective: The purpose of this study was to examine the influence of a novel "floatation-restricted environmental stimulation therapy" (floatation-REST) on growth hormone responses to an intense resistance exercise stress.

Design: Nine resistance trained men (age: 23.4 ± 2.5 yrs.; height: 175.3 ± 5.4 cm; body mass: 85.3 ± 7.9 kg) completed a balanced, crossover-controlled study design with two identical exercise trials, differing only in post-exercise recovery intervention (i.e., control or floatation-REST). A two-week washout period was used between experimental conditions. Plasma lactate was measured pre-exercise, immediately post-exercise and after the 1 h. recovery interventions. Plasma iGH was measured pre-exercise, immediately-post exercise, and after the recovery intervention, as well as 24 h and 48 h after the exercise test. The bGH-L was measured only at pre-exercise and following each recovery intervention.

Results: For both experimental conditions, a significant (P ≤ 0.05) increase in lactate concentrations were observed immediately post-exercise (~14 mmol • L-1) and remained slightly elevated after the recovery condition. The same pattern of responses was observed for iGH with no differences from resting values at 24 and 48 h of recovery. The bGH-L showed no exercise-induced changes following recovery with either treatment condition, however concentration values were dramatically lower than ever reported.

Conclusion: The use of floatation-REST therapy immediately following intense resistance exercise does not appear to influence anterior pituitary function in highly resistance trained men. However, the lower values of bGH suggest dramatically different molecular processing mechanisms at work in this highly trained population.
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http://dx.doi.org/10.1016/j.ghir.2020.101355DOI Listing
December 2020

From bedside to battlefield: intersection of ketone body mechanisms in geroscience with military resilience.

Geroscience 2021 06 2;43(3):1071-1081. Epub 2020 Oct 2.

Buck Institute for Research on Aging, Novato, CA, USA.

Ketone bodies are endogenous metabolites that are linked to multiple mechanisms of aging and resilience. They are produced by the body when glucose availability is low, including during fasting and dietary carbohydrate restriction, but also can be consumed as exogenous ketone compounds. Along with supplying energy to peripheral tissues such as brain, heart, and skeletal muscle, they increasingly are understood to have drug-like protein binding activities that regulate inflammation, epigenetics, and other cellular processes. While these energy and signaling mechanisms of ketone bodies are currently being studied in a variety of aging-related diseases such as Alzheimer's disease and type 2 diabetes mellitus, they may also be relevant to military service members undergoing stressors that mimic or accelerate aging pathways, particularly traumatic brain injury and muscle rehabilitation and recovery. Here we summarize the biology of ketone bodies relevant to resilience and rehabilitation, strategies for translational use of ketone bodies, and current clinical investigations in this area.
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http://dx.doi.org/10.1007/s11357-020-00277-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190215PMC
June 2021

A ketogenic diet combined with exercise alters mitochondrial function in human skeletal muscle while improving metabolic health.

Am J Physiol Endocrinol Metab 2020 12 28;319(6):E995-E1007. Epub 2020 Sep 28.

OSU Interdisciplinary PhD Program in Nutrition, Department of Human Sciences, The Ohio State University, Columbus, Ohio.

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-wk supervised exercise program after self-selection into a ketogenic diet (KD, = 15) group or maintenance of their habitual mixed diet (MD, = 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 with MD, the KD resulted in increased whole body resting fat oxidation ( < 0.001) and decreased fasting insulin ( = 0.019), insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), = 0.022], and visceral fat ( < 0.001). The KD altered mitochondrial function as evidenced by increases in mitochondrial respiratory control ratio (19%, = 0.009), ATP production (36%, = 0.028), and ATP/HO (36%, = 0.033) with the fat-based substrate. ATP production with the ketone-based substrate was four to eight times lower than with other substrates, indicating minimal oxidation. The KD resulted in a small decrease in muscle glycogen (14%, = 0.035) and an increase in muscle triglyceride (81%, = 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.
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http://dx.doi.org/10.1152/ajpendo.00305.2020DOI Listing
December 2020

Low carbohydrate diet: are concerns with saturated fat, lipids, and cardiovascular disease risk justified?

Curr Opin Endocrinol Diabetes Obes 2020 10;27(5):291-300

Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA.

Purpose Of Review: There is an extensive literature on the efficacy of the low carbohydrate diet (LCD) for weight loss, and in the improvement of markers of the insulin-resistant phenotype, including a reduction in inflammation, atherogenic dyslipidemia, hypertension, and hyperglycemia. However, critics have expressed concerns that the LCD promotes unrestricted consumption of saturated fat, which may increase low-density lipoprotein (LDL-C) levels. In theory, the diet-induced increase in LDL-C increases the risk of cardiovascular disease (CVD). The present review provides an assessment of concerns with the LCD, which have focused almost entirely on LDL-C, a poor marker of CVD risk. We discuss how critics of the LCD have ignored the literature demonstrating that the LCD improves the most reliable CVD risk factors.

Recent Findings: Multiple longitudinal clinical trials in recent years have extended the duration of observations on the safety and effectiveness of the LCD to 2-3 years, and in one study on epileptics, for 10 years.

Summary: The present review integrates a historical perspective on the LCD with a critical assessment of the persistent concerns that consumption of saturated fat, in the context of an LCD, will increase risk for CVD.
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http://dx.doi.org/10.1097/MED.0000000000000568DOI Listing
October 2020

Dietary Recommendations for Familial Hypercholesterolaemia: an Evidence-Free Zone.

BMJ Evid Based Med 2020 Jul 5. Epub 2020 Jul 5.

Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA.

We have evaluated dietary recommendations for people diagnosed with familial hypercholesterolaemia (FH), a genetic condition in which increased low-density lipoprotein cholesterol (LDL-C) is associated with an increased risk for coronary heart disease (CHD). Recommendations for FH individuals have emphasised a low saturated fat, low cholesterol diet to reduce their LDL-C levels. The basis of this recommendation is the 'diet-heart hypothesis', which postulates that consumption of food rich in saturated fat increases serum cholesterol levels, which increases risk of CHD. We have challenged the rationale for FH dietary recommendations based on the absence of support for the diet-heart hypothesis, and the lack of evidence that a low saturated fat, low cholesterol diet reduces coronary events in FH individuals. As an alternative approach, we have summarised research which has shown that the subset of FH individuals that develop CHD exhibit risk factors associated with an insulin-resistant phenotype (elevated triglycerides, blood glucose, HbA1c), obesity, hyperinsulinaemia, high-sensitivity C reactive protein, hypertension) or increased susceptibility to develop coagulopathy. The insulin-resistant phenotype, also referred to as the metabolic syndrome, manifests as carbohydrate intolerance, which is most effectively managed by a low carbohydrate diet (LCD). Therefore, we propose that FH individuals with signs of insulin resistance should be made aware of the benefits of an LCD. Our assessment of the literature provides the rationale for clinical trials to be conducted to determine if an LCD would prove to be effective in reducing the incidence of coronary events in FH individuals which exhibit an insulin-resistant phenotype or hypercoagulation risk.
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http://dx.doi.org/10.1136/bmjebm-2020-111412DOI Listing
July 2020

Saturated Fats and Health: A Reassessment and Proposal for Food-Based Recommendations: JACC State-of-the-Art Review.

J Am Coll Cardiol 2020 08 17;76(7):844-857. Epub 2020 Jun 17.

Department of Pediatrics, University of California-San Francisco, San Francisco, California; Department of Medicine, University of California-San Francisco, San Francisco, California.

The recommendation to limit dietary saturated fatty acid (SFA) intake has persisted despite mounting evidence to the contrary. Most recent meta-analyses of randomized trials and observational studies found no beneficial effects of reducing SFA intake on cardiovascular disease (CVD) and total mortality, and instead found protective effects against stroke. Although SFAs increase low-density lipoprotein (LDL) cholesterol, in most individuals, this is not due to increasing levels of small, dense LDL particles, but rather larger LDL particles, which are much less strongly related to CVD risk. It is also apparent that the health effects of foods cannot be predicted by their content in any nutrient group without considering the overall macronutrient distribution. Whole-fat dairy, unprocessed meat, and dark chocolate are SFA-rich foods with a complex matrix that are not associated with increased risk of CVD. The totality of available evidence does not support further limiting the intake of such foods.
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http://dx.doi.org/10.1016/j.jacc.2020.05.077DOI Listing
August 2020

Resistance Training and Milk-Substitution Enhance Body Composition and Bone Health in Adolescent Girls.

J Am Coll Nutr 2021 Mar-Apr;40(3):193-210. Epub 2020 Jun 10.

Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA.

Increased soft-drink consumption has contributed to poor calcium intake with 90% of adolescent girls consuming less than the RDA for calcium. The purpose of this investigation was to determine the independent and additive effects of two interventions (milk and resistance training) on nutrient adequacy, body composition, and bone health in adolescent girls. The experimental design consisted of four experimental groups of adolescent girls 14-17 years of age: (1) Milk + resistance training [MRT];  = 15; (2) Resistance training only [RT];  = 15; (3) Milk only [M]  = 20; (4) Control [C]  = 16. A few significant differences were observed at baseline between the groups for subject characteristics. Testing was performed pre and post-12 week training period for all groups. Milk was provided (3, 8 oz servings) for both the MRT and the M groups. The MRT group and the RT groups performed a supervised periodized resistance training program consisting of supervised one-hour exercise sessions 3 d/wk (M, W, F) for 12 wk. Baseline dietary data was collected utilizing the NUT-P-FFQ and/or a 120 item FFQ developed by the Fred Hutchinson Cancer Research Center (Seattle, Washington). Body composition was measured in the morning after an overnight fast using dual-energy X-ray absorptiometry (DXA) with a total body scanner (Prodigy, Lunar Corporation, Madison, WI). A whole body scan for bone density and lumbar spine scans were performed on all subjects. Maximal strength of the upper and lower body was assessed via a one-repetition maximum (1-RM) squat and bench press exercise protocols. Significance was set at  ≤ 0.05. Significant differences in nutrient intakes between groups generally reflected the nutrient composition of milk with greater intakes of protein and improved nutrient adequacy for several B vitamins, vitamin A, vitamin D, calcium, magnesium, phosphorus, potassium, and zinc. Mean calcium intake was 758 and 1581 mg/d, in the non-milk and milk groups, respectively, with 100% of girls in the milk groups consuming > RDA of 1300 mg/d. There were no effects of milk on body composition or muscle performance, but resistance training had a main effect and significantly increased body mass, lean body mass, muscle strength, and muscle endurance. There was a main effect of milk and resistance training on several measures of bone mineral density (BMD). Changes in whole body BMD in the M, RT, MRT, and CON were 0.45, 0.52, 1.32, and -0.19%, respectively ( < 0.01). Over the course of 12 weeks the effects of 1300 mg/d of calcium in the form of fluid milk combined with a heavy resistance training program resulted in the additive effects of greater nutrient adequacy and BMD in adolescent girls. While further studies are needed, combining increased milk consumption with resistance training appears to optimize bone health in adolescent girls.
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http://dx.doi.org/10.1080/07315724.2020.1770636DOI Listing
June 2020

A Pre-Workout Supplement of Ketone Salts, Caffeine, and Amino Acids Improves High-Intensity Exercise Performance in Keto-Naïve and Keto-Adapted Individuals.

J Am Coll Nutr 2020 May-Jun;39(4):290-300. Epub 2020 Apr 24.

Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA.

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. 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 = 12) or a ketogenic diet (Keto-Adapted; n = 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. Circulating total BHB concentrations increased rapidly after KCA ingestion in KN (154 to 732 μM) and KA (848 to 1,973 μM) 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). 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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http://dx.doi.org/10.1080/07315724.2020.1752846DOI Listing
July 2021

Quantification of Human Central Adipose Tissue Depots: An Anatomically Matched Comparison Between DXA and MRI.

Tomography 2019 12;5(4):358-366

Dorothy M. Davis Heart & Lung Research Institute, and.

Excess visceral adipose tissue (VAT) and VAT volume relative to subcutaneous adipose tissue (SAT) are associated with elevated health risks. This study compares fat measurements by dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI). In total, 21 control subjects (Control) and 16 individuals with metabolic syndrome (MetSyn) were scanned by DXA and MRI. The region measured by MRI was matched to the android region defined by DXA, and MRI reproducibility was also evaluated. In addition, liver fat fraction was quantified via MRI and whole-body fat by DXA. VAT measurements are interchangeable between DXA and MRI in the Control (R = 0.946), MetSyn (R = 0.968), and combined cohort (R = 0.983). VAT/SAT ratio did not differ in the Control group ( = .10), but VAT/SAT ratio measured by DXA was significantly higher in the MetSyn group ( < .01) and the combined ( = .03) cohort. Intraobserver (ICC = 0.998) and interobserver (ICC = 0.977) reproducibility of MRI VAT measurements was excellent. Liver fat fraction by MRI was higher ( = .001) in MetSyn (12.4% ± 7.6%) than in controls (2.6% ± 2.2%), as was whole-body fat percentage by DXA ( = .001) between the MetSyn (42.0% ± 8.1%) and Control groups (26.7% ± 6.9%). DXA and MRI VAT are interchangeable when measured over an anatomically matched region of the abdomen, while SAT and VAT/SAT ratio differ between the 2 modalities.
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http://dx.doi.org/10.18383/j.tom.2019.00018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935994PMC
December 2019

Extended Ketogenic Diet and Physical Training Intervention in Military Personnel.

Mil Med 2019 10;184(9-10):199-200

United States Army Special Operations Command, Bragg, NC.

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http://dx.doi.org/10.1093/milmed/usz184DOI Listing
October 2019

Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-Year Non-randomized Clinical Trial.

Front Endocrinol (Lausanne) 2019 5;10:348. Epub 2019 Jun 5.

Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States.

Studies on long-term sustainability of low-carbohydrate approaches to treat diabetes are limited. We previously reported the effectiveness of a novel digitally-monitored continuous care intervention (CCI) including nutritional ketosis in improving weight, glycemic outcomes, lipid, and liver marker changes at 1 year. Here, we assess the effects of the CCI at 2 years. An open label, non-randomized, controlled study with 262 and 87 participants with T2D were enrolled in the CCI and usual care (UC) groups, respectively. Primary outcomes were retention, glycemic control, and weight changes at 2 years. Secondary outcomes included changes in body composition, liver, cardiovascular, kidney, thyroid and inflammatory markers, diabetes medication use and disease status. Reductions from baseline to 2 years in the CCI group resulting from intent-to-treat analyses included: HbA1c, fasting glucose, fasting insulin, weight, systolic blood pressure, diastolic blood pressure, triglycerides, and liver alanine transaminase, and HDL-C increased. Spine bone mineral density in the CCI group was unchanged. Use of any glycemic control medication (excluding metformin) among CCI participants declined (from 55.7 to 26.8%) including insulin (-62%) and sulfonylureas (-100%). The UC group had no changes in these parameters (except uric acid and anion gap) or diabetes medication use. There was also resolution of diabetes (reversal, 53.5%; remission, 17.6%) in the CCI group but not in UC. All the reported improvements had < 0.00012. The CCI group sustained long-term beneficial effects on multiple clinical markers of diabetes and cardiometabolic health at 2 years while utilizing less medication. The intervention was also effective in the resolution of diabetes and visceral obesity with no adverse effect on bone health. Clinicaltrials.gov NCT02519309.
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http://dx.doi.org/10.3389/fendo.2019.00348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561315PMC
June 2019

Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss.

JCI Insight 2019 06 20;4(12). Epub 2019 Jun 20.

Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA.

BACKGROUNDMetabolic 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.METHODSIndividuals 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.RESULTSDespite 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.CONCLUSIONConsistent 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.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT02918422.FUNDINGDairy Management Inc. and the Dutch Dairy Association.
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http://dx.doi.org/10.1172/jci.insight.128308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629108PMC
June 2019

Changes of Hydration Measures in Elite National Collegiate Athletic Association Division I Wrestlers.

Int J Sports Physiol Perform 2019 Oct 2:1-4. Epub 2019 Oct 2.

Purpose: To evaluate the changes in the state of hydration in elite National Collegiate Athletic Association (NCAA) Division I college wrestlers during and after a season.

Methods: Ohio State University wrestling team members (N = 6; mean [SD] age = 19.6 [1.1] y; height = 171.6 [2.9] cm; body mass = 69.5 [8.1] kg) gave informed consent to participate in the investigation with measurements (ie, body mass, urine-specific gravity [USG; 2 methods], Visual Analog Scale thirst scale, plasma osmolality) obtained during and after the season.

Results: Measurements for USG, regardless of methods, were not significantly different between visits, but plasma osmolality was significantly (P = .001) higher at the beginning of the season-295.5 (4.9) mOsm·kg-1 compared with 279.6 (6.1) mOsm·kg-1 after the season. No changes in thirst ratings were observed, and the 2 measures of USG were highly correlated (r > .9, P = .000) at each time point, but USG and plasma osmolality were not related.

Conclusions: A paradox in the clinical interpretation of euhydration in the beginning of the season was observed with the USG, indicating that the wrestlers were properly hydrated, while the plasma osmolality showed they were not. Thus, the tracking of hydration status during the season is a concern when using only NCAA policies and procedures. The wrestlers did return to normal euhydration levels after the season on both biomarkers, which is remarkable, as previous studies have indicated that this may not happen because of the reregulation of the osmol-regulatory center in the brain.
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http://dx.doi.org/10.1123/ijspp.2019-0059DOI Listing
October 2019

Extended Ketogenic Diet and Physical Training Intervention in Military Personnel.

Mil Med 2019 10;184(9-10):e538-e547

Department of Human Sciences, The Ohio State University, 305 Annie and John Glenn Avenue, Columbus, OH.

Introduction: Ketogenic diets (KDs) that elevate ketones into a range referred to as nutritional ketosis represent a possible nutrition approach to address the emerging physical readiness and obesity challenge in the military. An emerging body of evidence demonstrates broad-spectrum health benefits attributed to being in nutritional ketosis, but no studies have specifically explored the use of a KD in a military population using daily ketone monitoring to personalize the diet prescription.

Materials And Methods: To evaluate the feasibility, metabolic, and performance responses of an extended duration KD, healthy adults (n = 29) from various military branches participated in a supervised 12-wk exercise training program. Fifteen participants self-selected to an ad libitum KD guided by daily measures of capillary blood ketones and 14 continued their normal mixed diet (MD). A battery of tests were performed before and after the intervention to assess changes in body mass, body composition, visceral fat, liver fat, insulin sensitivity, resting energy metabolism, and physical performance.

Results: All KD subjects were in nutritional ketosis during the intervention as assessed by daily capillary beta-hydroxybutyrate (βHB) (mean βHB 1.2 mM reported 97% of all days) and showed higher rates of fat oxidation indicative of keto-adaptation. Despite no instruction regarding caloric intake, the KD group lost 7.7 kg body mass (range -3.5 to -13.6 kg), 5.1% whole-body percent fat (range -0.5 to -9.6%), 43.7% visceral fat (range 3.0 to -66.3%) (all p < 0.001), and had a 48% improvement in insulin sensitivity; there were no changes in the MD group. Adaptations in aerobic capacity, maximal strength, power, and military-specific obstacle course were similar between groups (p > 0.05).

Conclusions: US military personnel demonstrated high adherence to a KD and showed remarkable weight loss and improvements in body composition, including loss of visceral fat, without compromising physical performance adaptations to exercise training. Implementation of a KD represents a credible strategy to enhance overall health and readiness of military service members who could benefit from weight loss and improved body composition.
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http://dx.doi.org/10.1093/milmed/usz046DOI Listing
October 2019

Post hoc analyses of surrogate markers of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in patients with type 2 diabetes in a digitally supported continuous care intervention: an open-label, non-randomised controlled study.

BMJ Open 2019 02 25;9(2):e023597. Epub 2019 Feb 25.

Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Objective: One year of comprehensive continuous care intervention (CCI) through nutritional ketosis improves glycosylated haemoglobin(HbA1c), body weight and liver enzymes among patients with type 2 diabetes (T2D). Here, we report the effect of the CCI on surrogate scores of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis.

Methods: This was a non-randomised longitudinal study, including adults with T2D who were self-enrolled to the CCI (n=262) or to receive usual care (UC, n=87) during 1 year. An NAFLD liver fat score (N-LFS) >-0.640 defined the presence of fatty liver. An NAFLD fibrosis score (NFS) of >0.675 identified subjects with advanced fibrosis. Changes in N-LFS and NFS at 1 year were the main endpoints.

Results: At baseline, NAFLD was present in 95% of patients in the CCI and 90% of patients in the UC. At 1 year, weight loss of ≥5% was achieved in 79% of patients in the CCI versus 19% of patients in UC (p<0.001). N-LFS mean score was reduced in the CCI group (-1.95±0.22, p<0.001), whereas it was not changed in the UC (0.47±0.41, p=0.26) (CCI vs UC, p<0.001). NFS was reduced in the CCI group (-0.65±0.06, p<0.001) compared with UC (0.26±0.11, p=0.02) (p<0.001 between two groups). In the CCI group, the percentage of individuals with a low probability of advanced fibrosis increased from 18% at baseline to 33% at 1 year (p<0.001).

Conclusions: One year of a digitally supported CCI significantly improved surrogates of NAFLD and advanced fibrosis in patients with T2D.

Trial Registration Number: NCT02519309; Results.
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http://dx.doi.org/10.1136/bmjopen-2018-023597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398805PMC
February 2019

Improvement in patient-reported sleep in type 2 diabetes and prediabetes participants receiving a continuous care intervention with nutritional ketosis.

Sleep Med 2019 03 3;55:92-99. Epub 2019 Jan 3.

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address:

Objective: Sleep disruption is frequently associated with type 2 diabetes (T2D) and hyperglycemia. We recently reported the effectiveness of a continuous care intervention (CCI) emphasizing nutritional ketosis for improving HbA1c, body weight and cardiovascular risk factors in T2D patients. The present study assessed the effect of this CCI approach on sleep quality using a subjective patient-reported sleep questionnaire.

Methods: A non-randomized, controlled longitudinal study; 262 T2D and 116 prediabetes patients enrolled in the CCI and 87 separately recruited T2D patients continued usual care (UC) treatment. Patients completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire. A PSQI score of >5 (scale 0 to 21) was used to identify poor sleepers.

Results: Global sleep quality improved in the CCI T2D (p < 0.001) and prediabetes (p < 0.001) patients after one year of intervention. Subjective sleep quality (component 1), sleep disturbance (component 5) and daytime dysfunction (component 7), also showed improvements in the CCI T2D (p < 0.01 for sleep quality and sleep disturbance; and p < 0.001 for daytime dysfunction) and prediabetes patients (p < 0.001 for all three components); compared to the UC T2D group after one year. The proportion of patients with poor sleep quality was significantly reduced after one year of CCI (T2D; from 68.3% at baseline to 56.5% at one year, p = 0.001 and prediabetes; from 77.9% at baseline to 48.7% at one year, p < 0.001).

Conclusion: This study demonstrates improved sleep quality as assessed by PSQI in patients with T2D and prediabetes undergoing CCI including nutritional ketosis but not in T2D patients receiving UC. The dietary intervention benefited both sleep quality and the severity of T2D symptoms suggesting that nutritional ketosis improves overall health via multiple mechanisms.
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http://dx.doi.org/10.1016/j.sleep.2018.12.014DOI Listing
March 2019

Dietary fat: From foe to friend?

Science 2018 11;362(6416):764-770

Cancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

For decades, dietary advice was based on the premise that high intakes of fat cause obesity, diabetes, heart disease, and possibly cancer. Recently, evidence for the adverse metabolic effects of processed carbohydrate has led to a resurgence in interest in lower-carbohydrate and ketogenic diets with high fat content. However, some argue that the relative quantity of dietary fat and carbohydrate has little relevance to health and that focus should instead be placed on which particular fat or carbohydrate sources are consumed. This review, by nutrition scientists with widely varying perspectives, summarizes existing evidence to identify areas of broad consensus amid ongoing controversy regarding macronutrients and chronic disease.
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http://dx.doi.org/10.1126/science.aau2096DOI Listing
November 2018

Dairy milk proteins attenuate hyperglycemia-induced impairments in vascular endothelial function in adults with prediabetes by limiting increases in glycemia and oxidative stress that reduce nitric oxide bioavailability.

J Nutr Biochem 2019 01 25;63:165-176. Epub 2018 Sep 25.

Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA. Electronic address:

Postprandial hyperglycemia (PPH) transiently impairs vascular endothelial function (VEF) in an oxidative stress-dependent manner by decreasing nitric oxide (NO) bioavailability. Dairy milk and its proteins attenuate PPH, but whether this improves VEF is unknown. We hypothesized that dairy milk, mediated by its whey and/or casein proteins, improves VEF by attenuating PPH-induced oxidative stress that otherwise decreases NO bioavailability. A randomized, cross-over trial was conducted in adults with prediabetes (n=23) who ingested glucose (75 g, GLU) alone or with 473 mL of non-fat dairy milk (MILK) or isonitrogenous (16.5 g) amounts of whey (WHEY) or casein (CASEIN) in 473 mL of water. Prior to and at 30 min intervals for 180 min postprandially, we assessed brachial artery flow-mediated dilation (FMD) and measured biomarkers of glycemic control, oxidative stress, and NO homeostasis. FMD decreased to the greatest extent during GLU, which was similarly improved in dairy trials. Compared with GLU, AUCs for glucose, malondialdehyde, F-isoprostanes, methylglyoxal, and endothelin-1 were similarly lower in dairy trials. Plasma arginine and NO metabolites were greater but methylated arginine metabolites were lower in dairy trials compared with GLU. Postprandial insulin, lipids, and tetrahydrobiopterin redox status did not differ among trials. Thus, dairy milk, mediated by its whey and casein proteins, attenuates PPH-mediated impairments in VEF by limiting oxidative stress. This improves NO bioavailability to the vascular endothelium by increasing arginine availability and limiting competitive inhibition on NO biosynthesis by asymmetric dimethylarginine. These findings support observational studies that dairy milk lowers cardiovascular disease risk.
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http://dx.doi.org/10.1016/j.jnutbio.2018.09.018DOI Listing
January 2019