Eating at the Right Time - A Novel Approach to Correct Non-Dipping Blood Pressure

Blood pressure (BP), among many physiological parameters, undergoes daily oscillations: blood pressure is lowest at night (nocturnal dip) and rises before awakening (morning surge). Such BP circadian organization is essential for optimum health. Diabetic patients have a high prevalence of BP circadian rhythm disruption mostly manifested as increased night time BP or non-dipping profile [1, 2]. Accumulating clinical studies demonstrated a striking pathophysiological link between end-organ damage and nondipping BP in diabetic patients [2-6]. Moreover, treatment with .1 hypertension medications at bedtime, compared with all medications upon waking, resulted in improved ambulatory blood pressure control and significantly reduced cardiovascular mortality [7]. Recent studies demonstrated that, in addition to light, food intake is a potent external cue that entrains endogenous clocks and circadian rhythm. Time restricted feeding (TRF) is one type of dietary regimen that involves limiting daily intake of food and caloric beverages to a certain time window, for example, 4 to 12 hours, without changing the type of food or the total caloric intake. In animal studies, timerestricted feeding has been shown to entrain endogenous clocks and metabolism [8-10]. Interestingly, active dark phase-restricted feeding exerts numerous health benefits. It prevents metabolic diseases in mice fed high fat diet, high fructose diet, or high-fat-plus-high fructose-diets [11, 12]; improves diurnal dynamics of the gut microbiome [13], and attenuates age-related cardiac decline in drosophila [14]. Moreover, our preliminary studies clearly demonstrated active phase restricted feeding restored the severely disrupted BP circadian rhythm to normal level in type 2 diabetic/obese db/db mice. The BP circadian rhythm recovery is associated with improvements of metabolic profiles and insulin sensitivity. Such fantastic health benefits of active phase restricted feeding in animal models begs for an investigation in a human population to test whether time restricted feeding offers similar tremendous health benefits. In support of the potential benefits of time-restricted food intake in diabetic patients, the frequency of night. eating behavior is higher in diabetic patients compared to healthy controls and is associated with adverse outcomes [15]. This proposal will test if time-restricted food intake has BP and metabolic benefits in humans. The central hypothesis is that nighttime eating increases the prevalence of non-dipping BP, and that daytime restricted food intake will restore normal BP dipping at night. This hypothesis will be tested in the following two aims. Aim 1: To determine if nighttime eating correlates with non-dipping BP. The circadian rhythms of BP, temperature and physical activity will be measured by wearable devices for 48 hours in obese pre-diabetic and diabetic subjects. Time of food intake will be recorded in a patient logbook and verified by use of a continuous glucose monitoring device. The circadian rhythm phase, amplitude and period length of BP, temperature and activity will be correlated with timing of food intake. Aim 2: To determine if daytime restricted food intake improves non-dipping BP. Subjects from aim 1 who are nighttime eaters (both dippers and non-dippers) will undergo a 6 week period of time restricted feeding (no change in total caloric intake) and circadian rhythms reassessed at 3 and 6 weeks using the wearable devices. Cardiovascular diseases are the most common causes of morbidity and mortality in diabetic patients. Non-dipping BP is associated with increased cardiovascular events. The proposed study is highly significant as it will provide a proof-of-principal result as to whether the tremendous heath benefit of timerestricted food intake approach observed in animal models is applicable to human patients. Compared with drug therapy, the strategy of time restricted feeding offers multiple benefits with minimal side effects. Animal studies suggest that time restricted feeding can confer additional benefits beyond BP circadian rhythm including potential effects on metabolism and insulin sensitivity. Furthermore, time-restricted food intake is highly innovative as it de-emphasizes caloric restriction and nutrient composition and thus is a readily adoptable lifestyle modification and easier than other dietary interventions or restrictions. Furthermore, if BP control can be obtained through time restricted feeding this could lead to lower medication use, which will decrease costs and side effects.