Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry. We found a significant fold increase in the levels of several tumor suppressor and DNA repair gene protein products (GP)s at the end of 4th week during 4-week intermittent fasting (CALU, INTS6, KIT, CROCC, PIGR), and 1 week after 4-week intermittent fasting (CALU, CALR, IGFBP4, SEMA4B) compared with the levels before 4-week intermittent fasting. We also found a significant reduction in the levels of tumor promoter GPs at the end of 4th week during 4-week intermittent fasting (POLK, CD109, CAMP, NIFK, SRGN), and 1 week after 4-week intermittent fasting (CAMP, PLAC1) compared with the levels before 4-week intermittent fasting. Fasting from dawn to sunset for four weeks also induced an anti-diabetes proteome response by upregulating the key regulatory proteins of insulin signaling at the end of 4th week during 4-week intermittent fasting (VPS8, POLRMT, IGFBP-5) and 1 week after 4-week intermittent fasting (PRKCSH), and an anti-aging proteome response by upregulating H2B histone proteins 1 week after 4-week intermittent fasting. Subjects had a significant reduction in body mass index, waist circumference, and improvement in blood pressure that co-occurred with the anticancer, anti-diabetes, and anti-aging serum proteome response. These findings suggest that intermittent fasting from dawn to sunset actively modulates the respective genes and can be an adjunct treatment in metabolic syndrome. Further studies are needed to test the intermittent fasting from dawn to sunset in the prevention and treatment of metabolic syndrome-induced cancers.

Background Brain-derived neurotrophic factor (BDNF) is a key neurotrophin that regulates food intake and energy hemostasis. BDNF also promotes neurogenesis, neuroplasticity, and neuroprotection. There are conflicting reports regarding how intermittent fasting affects circulating BDNF levels. We tested the hypothesis that 4-week intermittent fasting from dawn to sunset (4-week-IF) would decrease circulating BDNF levels in subjects with metabolic syndrome and healthy subjects. Methods We conducted pilot studies in subjects with metabolic syndrome and healthy subjects who fasted from dawn to sunset for more than 14 h for four consecutive weeks. We measured serum BDNF levels and metabolic parameters before 4-week-IF, at the end of 4th week during 4-week-IF, and one week after 4-week-IF. Results We enrolled 28 subjects, 14 with metabolic syndrome (women/men:6/8) with a mean age of 59 years and 14 healthy subjects (women/men:1/13) with a mean age of 32 years. Overall, BDNF levels decreased at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF (mean paired difference = −98.5 ng/ml, P = 0.0006). When subjects with metabolic syndrome were compared with healthy subjects, subjects with metabolic syndrome had a lower mean paired reduction in BDNF levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF (BDNF mean paired difference = −27.6 ng/ml vs. −169.5 ng/ml, P = 0.003). Multivariate linear regression analysis showed a positive correlation between the change in tumor necrosis factor-alpha and change in BDNF levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF in subjects with metabolic syndrome (P = 0.040) and healthy subjects (P = 0.007). The change in weight and body mass index independently predicted the change in BDNF levels 1 week after 4-week-IF compared with the levels before 4-week-IF in subjects with metabolic syndrome. Conclusion Four-week-IF resulted in a reduction in the BDNF levels at the end of 4th week during 4-week-IF. Higher BDNF levels and a lower reduction in BDNF levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF in subjects with metabolic syndrome than healthy subjects suggest a potential BDNF resistance similar to insulin and leptin resistance in metabolic syndrome. A positive correlation between the change in BDNF and change in tumor necrosis factor-alpha levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF suggests that BDNF is a biomarker of inflammation and endothelial dysfunction in addition to its neurotrophic and anorexigenic features.

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Objectives: Four-hour gastric emptying scintigraphy (GES) is the recommended method to identify both adult and childhood gastroparesis (GP). Previous pediatric studies have, however, not used this standard. We sought to determine the characteristics and outcomes of children versus adolescents with GP using the 4-hour GES evaluation. Methods: We performed a retrospective chart review of pediatric patients diagnosed with GP by 4-hour GES (>10% retention at 4 hours). Demographics, body mass index, GP-related symptoms, comorbidities, etiologies, therapies (eg, medications), healthcare utilization, and response to therapy were captured systematically. Symptoms were compared from the initial versus last gastroenterology visit. Outcomes were categorized as no improvement; improvement (resolution of at least 1 symptom while remaining on therapy); and complete resolution of symptoms. Results: A total of 239 subjects (12.1 AE 4.1 years [mean AE standard deviation], 70% girls) were included. The identified characteristics of childhood GP were broad with idiopathic GP being the most common etiology. Outcomes over a median of 22 months (25%-75%: 9.0-45.5 months) were 34.8% no improvement, 34.8% some improvement, and 30.3% with complete symptom resolution. Compared to younger children, adolescents had a higher female predominance (P < 0.01) and were more likely to have nausea (P ¼ 0.006). Girls were more likely to have abdominal pain (P ¼ 0.001), nausea (P ¼ 0.03), and a documented diagnosis of dysautonomia (P ¼ 0.03). Boys were more likely to have regurgitation (P ¼ 0.006), gastroesophageal reflux disease (P ¼ 0.02), and rumination (P ¼ 0.02). Conclusions: Using the 4-hour GES standard, childhood GP has broad clinical characteristics and outcomes. There are several significant age-and sex-based differences in childhood GP.