Brain dopamine responses to ultra-processed milkshakes are highly variable and not significantly related to adiposity in humans.

Ultra-processed foods high in fat and sugar may be addictive, in part, due to their purported ability to induce an exaggerated postingestive brain dopamine response akin to drugs of abuse. Using standard [11C]raclopride positron emission tomography (PET) displacement methods used to measure brain dopamine responses to addictive drugs, we measured postingestive striatal dopamine responses to an ultra-processed milkshake high in fat and sugar in 50 young, healthy adults over a wide body mass index range (BMI 20-45 kg/m2). Surprisingly, milkshake consumption did not result in significant postingestive dopamine response in the striatum (p=0.62) nor any striatal subregion (p>0.33) and the highly variable interindividual responses were not significantly related to adiposity (BMI: r=0.076, p=0.51; %body fat: r=0.16, p=0.28). Thus, postingestive striatal dopamine responses to an ultra-processed milkshake were likely substantially smaller than many addictive drugs and below the limits of detection using standard PET methods.

Impact of systemic disease on CNS disease control after stereotactic radiosurgery to breast cancer brain metastases (The SYBRA Study).

The objective of the study is to assess impact of systemic disease (SD) status on overall survival and brain metastasis (BM) control, adopting a novel landmark approach to categorize SD among breast cancer (BC) patients. This single institution retrospective study included BCBM patients who have received stereotactic radiosurgery (SRS) to brain. Separate endpoints [CNS failure-free survival (cFFS), overall survival (OS)] were analyzed from each Landmark (LM): LM1 (3-months), LM2 (6-months). Patients were categorized into early and non-early progression (EP, NEP) groups depending on SD status before LMs. Median survivals from LM were assessed with Kaplan Meier plots, compared with Log-Rank test. EP was associated with worse median cFFS and OS vs NEP in both LM analyses (cFFS- LM1: 3.6 vs. 9.7 months, p = 0.0016; LM2: 2.3 vs. 12.5 months, p < 0.0001; OS- LM1: 3.6 vs. 24.3 months, p < 0.0001; LM2: 5.3 vs. 30.2 months, p < 0.0001). In multivariate analyses, EP was associated with shorter cFFS [LM1: Hazard Ratio (HR) with 95% confidence interval (CI) 3.16, 1.46-6.83, p = 0.0034; LM2: 5.32, 2.33-12.15, p = <0.0001] and shorter OS (LM1: HR with 95% CI 4.28, 1.98-9.12, p = 0.0002; LM2: 7.40, 3.10-17.63, p = <0.0001) vs NEP. Early systemic disease progressions after 1st SRS to brain is associated with worse cFFS and OS in patients with BCBM.

Striatal dopamine tone is positively associated with body mass index in humans as determined by PET using dual dopamine type-2 receptor antagonist tracers.

The relationship between adiposity and dopamine type-2 receptor binding potential (D2BP) in the human brain has been repeatedly studied for >20 years with highly discrepant results, likely due to variable methodologies and differing study populations. We conducted a controlled inpatient feeding study to measure D2BP in the striatum using positron emission tomography with both [18F]fallypride and [11C]raclopride in pseudo-random order in 54 young adults with a wide range of body mass index (BMI 20-44 kg/m2). Within-subject D2BP measurements using the two tracers were moderately correlated (r=0.47, p<0.001). D2BP was negatively correlated with BMI as measured by [11C]raclopride (r= -0.51; p<0.0001) but not [18F]fallypride (r=-0.01; p=0.92) and these correlation coefficients were significantly different from each other (p<0.001). Given that [18F]fallypride has greater binding affinity to dopamine type-2 receptors than [11C]raclopride, which is more easily displaced by endogenous dopamine, our results suggest that adiposity is positively associated with increased striatal dopamine tone.

Effect of a plant-based, low-fat diet versus an animal-based, ketogenic diet on ad libitum energy intake.

The carbohydrate-insulin model of obesity posits that high-carbohydrate diets lead to excess insulin secretion, thereby promoting fat accumulation and increasing energy intake. Thus, low-carbohydrate diets are predicted to reduce ad libitum energy intake as compared to low-fat, high-carbohydrate diets. To test this hypothesis, 20 adults aged 29.9 ± 1.4 (mean ± s.e.m.) years with body mass index of 27.8 ± 1.3 kg m-2 were admitted as inpatients to the National Institutes of Health Clinical Center and randomized to consume ad libitum either a minimally processed, plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with high glycemic load (85 g 1,000 kcal-1) or a minimally processed, animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with low glycemic load (6 g 1,000 kcal-1) for 2 weeks followed immediately by the alternate diet for 2 weeks. One participant withdrew due to hypoglycemia during the low-carbohydrate diet. The primary outcomes compared mean daily ad libitum energy intake between each 2-week diet period as well as between the final week of each diet. We found that the low-fat diet led to 689 ± 73 kcal d-1 less energy intake than the low-carbohydrate diet over 2 weeks (P < 0.0001) and 544 ± 68 kcal d-1 less over the final week (P < 0.0001). Therefore, the predictions of the carbohydrate-insulin model were inconsistent with our observations. This study was registered on ClinicalTrials.gov as NCT03878108 .