A schematic of interventions is shown in Fig. 1. The study was performed in a randomized cross-over design as part of a multi-disciplinary project evaluating the effects of simulated microgravity and hypocaloric nutrition on cardiovascular and sympathetic nervous function. Thus, information from several of the supporting references was derived from the current study design. The subjects participated in four study phases that were separated by at least 5 months to allow complete recovery of the participants, and each subject served as his own control. Each study phase started with a 9-day nutrition and physical activity adaptation period followed by a 14-day intervention period; in each of the 4 intervention periods the participants were exposed to either bedrest or ambulatory control conditions, while receiving either a tailored normocaloric or hypocaloric diet. Cardiovascular and sympathetic responses to the cold pressor test and handgrip exercise were investigated before the intervention and on day 14 of the intervention period. All four study phases were identical with respect to environmental conditions and study protocol; only the variables posture (bedrest or ambulation) and energy intake (normocaloric or hypocaloric) were changed. Fig. 1 Schematic of interventions. Each subject participated in a hypocaloric and normocaloric study phase in the 6° head-down bedrest condition and in a hypocaloric and normocaloric study phase in the upright mobile condition. Each phase, which was separated by at least 5 months, started with a 9-day nutrition and physical activity adaptation period followed by a 14-day intervention period. Handgrip and cold pressor tests were completed before and immediately after the intervention