Eating at the right time of day: an underappreciated lifestyle therapy for hypertension?

aily cycles of light and dark due to the rotation ofthe earth around its axis have dictated how life hasevolved on Earth. Organisms have thus developedthe ability to predict these 24-h cycles by developing anendogenous circadian clock, which is entrained to externalcues. In mammals, circadian rhythms are controlled andgeneratedbythecentralormastercircadianclocklocatedinthe suprachiasmatic nuclei (SCN)of the anterior hypothala-mus in the brain [1]. This master clock consists of multiplesingle-cellcircadianoscillatorsthataresynchronizedto24hby environmental factors, primarily dark/light and alsotemperature and food. The retina perceives the dark/lightcycleinformationandtransmitsthissignaltotheSCNviatheretinohypothalamic tract. The SCN then transmits theseinputs to peripheral oscillators located outside the SCN.Such peripheral oscillators exist in nearly all peripheraltissues such as liver, adipose, pancreas, muscle and blood.Therefore, circadian rhythms have been described for vir-tually all physiological and biochemical processes, includ-ing behavioural ones [2].The SCN may influence the cardiovascular systemprimarily through multisynaptic neural projections to theheart,adrenalcortex,kidneysandvasculatureandresultantneural or endocrine effects, and secondarily by circadianinfluences on behaviours such as sleep and activity andfeeding patterns [3]. Thus, the master SCN clock sendsperiodic signals to the peripheral oscillators in order toprevent dampening of circadian rhythms, but a complexreciprocal relationship seems also to exist. Indeed, alteredbehaviours, for example when sleeping or food intake isdesynchronized from normal circadian patterns, seem toaffect the peripheral oscillators or clocks in particular,resulting in metabolic processes that are decoupled fromthe primarily light-driven SCN [4,5]. In addition, the multi-plicityofperipheralclocksinthehumanorganismhasbeenfound to comprise networks that both control circadianprocessesandaretightlyconnectedtometabolicandneuralcontrol networks, such that disturbance of one affects theother. Hence, misalignment of circadian rhythms in theSCN and peripheral tissues may constitute an importantunderling factor for a variety of metabolic and vasculardisorders such as obesity, metabolic syndrome, diabetesand hypertension [4,6,7]. Adverse cardiometabolic end-points including higher glucose, insulin, leptin, ghrelin,glucagon-like peptide-1, cortisol, blood pressure (BP)and catecholamines have been reported as results ofmisalignments invoked by food intake/irregular meal fre-quency (for comprehensive reviews see, for instance[1,2,4]). This new evidence illustrates how knowledge onchronobiology, that is the circadian influences on mech-anisms involved in metabolic and cardiovascular disease,and their interaction with behavioural influences, may beimportant for optimizing preventive lifestyle measures orpharmacological therapy [8,9]. For instance, preventingadversebehaviouraltriggersatspecificvulnerablecircadiantimes [4] or prescribing ingestion of medicines at specifictimes in anticipation of vulnerable periods [9,10] maymaximize their beneficial effects. Currently, such timedmeasures or chronotherapy constitute new avenues ofresearchforthepreventionandtreatmentofmanydiseases,including asthma, arthritis, cancer and seasonal affectivedisorder [11].Chronotherapy has been recommended for the treat-ment of major cardiovascular risk factors such as hyperten-sion [11] and dyslipidaemia [10], though typically in thecontext of pharmacotherapy. Timing of meals may con-stitute one such lifestyle therapeutical tool as well. In fact,some form of dietary chronotherapy is already imple-mented in metabolic diseases such as diabetes, whereinthe timing of meals is particularly important, as patientsneed to coordinate insulin administration with calorieintake. Interestingly, in recognition of the chronobiologicalaspects of nutrition, Franz Halberg [12] called for researchon the ‘when to eat’ question more than two decades ago.Currently, the beneficial chronobiological effects of foodintake (e.g. meal time, frequency and regularity) are beingsubject of intensive research as a potential additional or