Abstract
BackgroundIntermittent fasting (IF) improves healthy lifespan in animals by a mechanism involving reduced oxidative damage and increased resistance to stress. However, no studies have evaluated the impact of controlled meal frequency on immune responses in human subjects.ObjectiveA study was conducted to establish the effects of controlled diets with different meal frequencies, but similar daily energy intakes, on cytokine production in healthy male and female subjects.DesignIn a crossover study design with an intervening washout period, healthy normal weight middle-age male and female subjects (n = 15) were maintained for 2 months on controlled on-site one meal per day (OMD) or three meals per day (TMD) isocaloric diets. Serum samples and peripheral blood mononuclear cells (PBMCs) culture supernatants from subjects were analyzed for the presence of inflammatory markers using a multiplex assay.ResultsThere were no significant differences in the inflammatory markers in the serum of subjects on the OMD or TMD diets. There was an increase in the capacity of PBMCs to produce cytokines in subjects during the first month on the OMD or TMD diets.Lower levels of TNF-α, IL-17, MCP-1 and MIP-1β were produced by PBMCs from subjects on the OMD versus TMD diet.ConclusionsPBMCs of subjects on controlled diets exhibit hypersensitivities to cellular stimulation suggesting that stress associated with altered eating behavior might affect cytokine production by immune cells upon stimulation. Moreover, stimulated PBMCs derived from healthy individuals on a reduced meal frequency diet respond with a reduced capability to produce cytokines.
Highlights
It has been hypothesized that due to limited availability of food throughout the majority of human evolution, the body was more adapted towards intermittent feeding rather than to regular meal intervals as currently practiced in the developed world [1]
There was an increase in the capacity of peripheral blood mononuclear cells (PBMCs) to produce cytokines in subjects during the first month on the one meal per day (OMD) or three meals per day (TMD) diets
C-reactive protein (CRP) levels were elevated in subjects when they were on the OMD diet compared to the TMD diet (Figure 1A)
Summary
It has been hypothesized that due to limited availability of food throughout the majority of human evolution, the body was more adapted towards intermittent feeding rather than to regular meal intervals as currently practiced in the developed world [1]. It has been suggested that a prominent immune-enhancing effect of CR on NK cells and CTL mediates, in part, the reduced incidence of tumors in mice maintained on CR diets [10,11]. Data from controlled studies in rodents suggest that intermittent fasting (IF) can protect against age-related diseases and can extend lifespan, and that at least some of the beneficial effects of IF may be independent of calorie intake [1,4]. Increasing evidence suggests that the signaling mechanisms that regulate energy metabolism and immune function are tightly coupled to each other [18,19]. Genomic profiling studies in rodents revealed that CR can reverse the increased inflammation associated with aging [22] and inhibit the release of proinflammatory mediators from macrophages [23]. No studies have evaluated the impact of controlled meal frequency on immune responses in human subjects
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