Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease

Abstract

Calorie restriction or changes in dietary composition can enhance healthy aging, but the inability of most subjects to adhere to chronic and extreme diets, as well as potentially adverse effects, limits their application. We randomized 100 generally healthy participants from the United States into two study arms and tested the effects of a fasting-mimicking diet (FMD)-low in calories, sugars, and protein but high in unsaturated fats-on markers/risk factors associated with aging and age-related diseases. We compared subjects who followed 3 months of an unrestricted diet to subjects who consumed the FMD for 5 consecutive days per month for 3 months. Three FMD cycles reduced body weight, trunk, and total body fat; lowered blood pressure; and decreased insulin-like growth factor 1 (IGF-1). No serious adverse effects were reported. After 3 months, control diet subjects were crossed over to the FMD program, resulting in a total of 71 subjects completing three FMD cycles. A post hoc analysis of subjects from both FMD arms showed that body mass index, blood pressure, fasting glucose, IGF-1, triglycerides, total and low-density lipoprotein cholesterol, and C-reactive protein were more beneficially affected in participants at risk for disease than in subjects who were not at risk. Thus, cycles of a 5-day FMD are safe, feasible, and effective in reducing markers/risk factors for aging and age-related diseases. Larger studies in patients with diagnosed diseases or selected on the basis of risk factors are warranted to confirm the effect of the FMD on disease prevention and treatment.

Fig. 1.. CONSORT diagram.

Consolidated Standards of Reporting Trials (CONSORT) diagram of 102 contacted subjects of which 100 were enrolled into the study two arms. Arm 1 (n = 48), the “control” group, maintained their normal caloric intake for a 3-month monitoring period. Data were collected at enrollment and again after 3 months. Participants in arm 2 (n = 52) started the FMD after randomization. The FMD is provided for 5 days per month for three consecutive cycles. Data were collected at enrollment, at the completion of the first FMD cycle but before resuming normal dietary intake, and also on average 5 days after subjects resumed their normal diet after the final FMD cycle. After the initial 3-month period, subjects in arm 1 also started the FMD. An optional follow-up visit in the clinic for analysis was offered to all participants about 3 months after the completion of the third FMD cycle.

Fig. 2.. Change analysis of metabolic variables during the randomization.

Effects on aging/disease markers and risk factors in all subjects who completed the randomized analysis in either the control arm or the FMD arm (5 to 7 days after the third cycle of FMD). (A) Body weight, (B) BMI, (C) total body fat, (D) trunk fat, (E) lean body mass, (F) waist circumference, (G) serum glucose level, (H) insulin-like growth factor 1, (I) systolic blood pressure, (J) diastolic blood pressure, (K) triglycerides, (L) total cholesterol, (M) LDL, (N) HDL, and (O) CRP were measured in both cohorts as described. The Δ change represents a comparison to baseline. All data are means ± SD. Between-arm comparisons were calculated using two-tailed two-sample equal variance t tests. For some of the 100 enrolled participants, the nurses were unable to collect all the samples/measurements from all subjects. We therefore excluded subjects with incomplete measurements from a particular marker group (see Table 2 for details). Abs, absolute; Rel, relative; BP, blood pressure.

Fig. 3.. Post hoc analysis of metabolic variables in subgroups identified by severity of risk factors.

Subjects from both study arms who completed three FMD cycles were post hoc stratified on the basis of being in either normal-risk or at-risk subgroups for factors associated with age-related diseases and conditions. The Δ change shown represents comparisons to baseline. All data are means ± SD. Between-arm comparisons were calculated using two-tailed two-sample equal variance t tests. One-way analysis of variance was used for the BMI groups (see Table 4 for details).