Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome

Abstract

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.

The effect of four-week intermittent fasting from dawn to sunset on circulating brain-derived neurotrophic factor levels in subjects with metabolic syndrome and healthy subjects

“…After obtaining approval from the Institutional Review Board of the Baylor College of Medicine (Protocol number H-31612) and informed consent from all subjects, we conducted pilot studies in subjects with metabolic syndrome and healthy subjects who observed the month of Ramadan in 2019 and 2018, respectively [ 16 , 17 ].…”

“…We previously reported the inclusion and exclusion criteria for both studies [ 16 , 17 ]. Briefly, for the study conducted on subjects with metabolic syndrome, we included those who were 18 years of age or older, agreed to have a FibroScan® [ 18 ] and planned to fast during the month of Ramadan [17] .…”

“…We previously reported the inclusion and exclusion criteria for both studies [ 16 , 17 ]. Briefly, for the study conducted on subjects with metabolic syndrome, we included those who were 18 years of age or older, agreed to have a FibroScan® [ 18 ] and planned to fast during the month of Ramadan [17] . Study exclusion criteria were the inability to consent, use of alcohol or recreational substances, pregnancy or breastfeeding, active cancer and infection, seizure disorder, and a cardiovascular event that occurred during the last six months before enrollment [ 17 ].…”

“…Subjects with metabolic syndrome fasted from dawn to sunset for more than 14 h daily for 29 days [ 17 ]. Healthy subjects fasted from dawn to sunset for more than 14 h daily for 30 days, excluding one subject who fasted for 26 days instead of 29 days [ 16 ].…”

“…Healthy subjects fasted from dawn to sunset for more than 14 h daily for 30 days, excluding one subject who fasted for 26 days instead of 29 days [ 16 ]. Both study cohorts had strict dry fasting (no food, drink or water) from dawn to sunset [ 16 , 17 ].…”