A randomized feasibility trial of medium chain triglyceride-supplemented ketogenic diet in people with Parkinson's disease.

BACKGROUND: A ketogenic diet (KD) may benefit people with neurodegenerative disorders marked by mitochondrial depolarization/insufficiency, including Parkinson's disease (PD). OBJECTIVE: Evaluate whether a KD supplemented by medium chain triglyceride (MCT-KD) oil is feasible and acceptable for PD patients. Furthermore, we explored the effects of MCT-KD on blood ketone levels, metabolic parameters, levodopa absorption, mobility, nonmotor symptoms, simple motor and cognitive tests, autonomic function, and resting-state electroencephalography (rsEEG). METHODS: A one-week in-hospital, double-blind, randomized, placebo-controlled diet (MCT-KD vs. standard diet (SD)), followed by an at-home two-week open-label extension. The primary outcome was KD feasibility and acceptability. The secondary outcome was the change in Timed Up & Go (TUG) on day 7 of the diet intervention. Additional exploratory outcomes included the N-Back task, Unified Parkinson's Disease Rating Scale, Non-Motor Symptom Scale, and rsEEG connectivity. RESULTS: A total of 15/16 subjects completed the study. The mean acceptability was 2.3/3, indicating willingness to continue the KD. Day 7 TUG time was not significantly different between the SD and KD groups. The nonmotor symptom severity score was reduced at the week 3 visit and to a greater extent in the KD group. UPDRS, 3-back, and rsEEG measures were not significantly different between groups. Blood ketosis was attained by day 4 in the KD group and to a greater extent at week 3 than in the SD group. The plasma levodopa metabolites DOPAC and dopamine both showed nonsignificant increasing trends over 3 days in the KD vs. SD groups. CONCLUSIONS: An MCT-supplemented KD is feasible and acceptable to PD patients but requires further study to understand its effects on symptoms and disease. TRIAL REGISTRATION: Trial Registration Number NCT04584346, registration dates were Oct 14, 2020 - Sept 13, 2022.

Proton MR Spectroscopy Measurements of White and Brown Adipose Tissue in Healthy Humans: Relaxation Parameters and Unsaturated Fatty Acids.

Background Activation of brown adipose tissue (BAT) in rodents increases lipolysis in white adipose tissue (WAT) and improves glucose tolerance. Adult humans can have metabolically active BAT. Implications for diabetes and obesity in humans require a better characterization of BAT in humans. Purpose To study fat depots with localized proton MR spectroscopy relaxometry and to identify differences between WAT and fluorine 18 fluorodeoxyglucose (FDG) PET/CT proven cold-activated BAT in humans. Materials and Methods Participants were consecutively enrolled in this prospective study (ClinicalTrials.gov identifiers: NCT01568671 and NCT01399385) from August 2016 to May 2019. Supraclavicular potential BAT regions were localized with MRI. Proton densities, T1, and T2 were measured with localized MR spectroscopy in potential BAT and in subcutaneous WAT. FDG PET/CT after cold stimulation was used to retrospectively identify active supraclavicular BAT or supraclavicular quiescent adipose tissue (QAT) regions. MR spectroscopy results from BAT and WAT were compared with grouped and paired tests. Results Of 21 healthy participants (mean age, 36 years ± 16 [standard deviation]; 13 men) FDG PET/CT showed active BAT in 24 MR spectroscopy-targeted regions in 16 participants (eight men). Four men had QAT. The T2 for methylene protons was shorter in BAT (mean, 69 msec ± 6, 24 regions) than in WAT (mean, 83 msec ± 3, 18 regions, P < .01) and QAT (mean, 78 msec ± 2, five regions, P < .01). A T2 cut-off value of 76 msec enabled the differentiation of BAT from WAT or QAT with a sensitivity of 85% and a specificity of 95%. Densities of protons adjacent and between double bonds were 33% and 24% lower, respectively, in BAT compared with those in WAT (P = .01 and P = .03, respectively), indicating a lower content of unsaturated and polyunsaturated fatty acids, respectively, in BAT compared with WAT. Conclusion Proton MR spectroscopy showed shorter T2 and lower unsaturated fatty acids in brown adipose tissue (BAT) than that in white adipose tissue in healthy humans. It was feasible to identify BAT with MR spectroscopy without the use of PET/CT or cold stimulation. © RSNA, 2021 See also the editorial by Barker in this issue. Online supplemental material is available for this article.

Relationship of Mindfulness to Distress and Cortisol Response in Adolescent Girls At-Risk for Type 2 Diabetes.

Altered stress response theoretically contributes to the etiology of cardiometabolic disease. Mindfulness may be a protective buffer against the effects of stress on health outcomes by altering how individuals evaluate and respond to stress. We engaged adolescent girls at risk for developing Type 2 diabetes in a cold-pressor test in order to determine the relationship of dispositional mindfulness to cortisol response and subjective stress, including perceived pain and unpleasantness during the stressor, and negative affect following the stressor. We also evaluated mindfulness as a moderator of psychological distress (depressive/anxiety symptoms) and stress response. Participants were 119 girls age 12-17 years with overweight/obesity, family history of diabetes, and mild-to-moderate depressive symptoms. Greater mindfulness was associated with less perceived pain and negative affect, but was unrelated to cortisol response to the stressor. Regardless of mindfulness, greater depressive/anxiety symptoms related to a more blunted cortisol response. Mindfulness might promote better distress tolerance in adolescents at risk for diabetes by altering how youth perceive and relate to acute stress, rather than through altering the physiological stress response. At all levels of mindfulness, depressive/anxiety symptoms relate to greater blunting of cortisol response. Findings contribute to emerging literature on the role of mindfulness in promoting the mental and physical health and well-being of individuals at risk for Type 2 diabetes.

Mindfulness and eating behavior in adolescent girls at risk for type 2 diabetes.

OBJECTIVE: The purpose of this investigation was to examine the relationship of dispositional mindfulness to binge eating and associated eating attitudes and behaviors among adolescent girls at risk for type 2 diabetes (T2D). METHODS: Participants were 114 overweight or obese adolescents enrolled in a study of girls with a family history of T2D and mild depressive symptoms. Adolescent self-reports of mindfulness, eating in the absence of hunger, and depressive symptoms were collected. An interview was administered to determine presence of binge eating episodes and a behavioral task was used to assess the reinforcing value of food relative to other nonsnack food rewards. Body composition was assessed using dual-energy X-ray absorptiometry. RESULTS: In analyses accounting for race, percent body fat, lean mass, height, age, and depressive symptoms, dispositional mindfulness was associated with a lower odds of binge eating (p = .002). Controlling for the same potential confounds, mindfulness was also inversely associated with eating concern, eating in the absence of hunger in response to fatigue/boredom, and higher food reinforcement relative to physical activity (all p < .05). DISCUSSION: In girls with a family history of T2D, independent of body composition and depressive symptoms, intraindividual differences in mindfulness are related to binge eating and associated attitudes and behaviors that may confer risk for obesity and metabolic problems. Further research is needed to determine the extent to which mindfulness plays a role in the etiology and/or maintenance of disinhibited eating in adolescents at risk for T2D.