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  • Systematic Review
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30 April 2026

41 Pages

Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures

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,
and
1
Faculty of Health Sciences, University of Zaragoza, 50009 Zaragoza, Spain
2
Department of Nutrition and Sustainable Animal Production, Estación Experimental del Zaidín (EEZ-CSIC), 18008 Granada, Spain
3
Aragon Health Service, 50017 Zaragoza, Spain
4
AgriFood Institute of Aragon (IA2), 50013 Zaragoza, Spain
Nutrients2026, 18(9), 1450;https://doi.org/10.3390/nu18091450
This article belongs to the Special Issue Nutrition and Care Strategies to Promote Healthy Aging and Prevent Chronic Diseases in Older Adults
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Abstract

Background/Objective: Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods: Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre–post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis. Results: Thirty-one studies were included; seven RCTs were eligible for network meta-analysis. ISF and TRE 16:8 were most effective for weight (ISF: −2.36 kg; TRE 16:8: −1.92 kg) and BMI reduction (−0.81 and −1.01 kg/m2) without lean mass loss. Findings on cardiometabolic parameters, mental health, and cognitive function are based on the narrative synthesis of individual studies. Long-term structured IF was associated with improvements in standardized cognitive performance assessed via validated instruments. However, very restrictive eating windows (≤10 h) and prolonged fasting (>12.38 h) were associated with adverse outcomes, including lower cognitive scores and 58% increased cardiovascular mortality. Conclusions: TRE 16:8 and ISF showed the strongest comparative evidence for weight reduction in the RCT-based NMA, with acceptable short-term safety profiles in the included trials. In the narrative review, these protocols were associated with clinically meaningful improvements in body weight, metabolic markers, and blood pressure while generally preserving lean muscle mass in older adults. The cardiovascular mortality risk associated with very restrictive eating windows may emphasize the importance of moderate fasting approaches in this vulnerable population. Further long-term research is needed to confirm optimal protocols and identify at-risk subgroups.

1. Introduction

Intermittent fasting (IF) is a temporal dietary pattern alternating periods of restricted caloric intake with unrestricted feeding [1]. Unlike continuous energy restriction, IF emphasizes timing and pattern of food intake rather than total energy or nutrients, representing an alternative approach for weight loss and metabolic health promotion [2,3].
The most studied IF protocols include time-restricted eating (TRE), which restricts intake to an 8–12 h daily window aligned with circadian rhythms [4]; alternate-day fasting (ADF), alternating between fasting and normal eating days [5]; and the 5:2 method, involving five normal eating days followed by two days of severe caloric restriction [6]. Each regimen differs in fasting duration, frequency, and circadian alignment, potentially leading to heterogeneous health effects.
Proposed mechanisms underlying IF benefits include metabolic switching—where glycogen depletion shifts energy metabolism from glucose to ketone bodies, enhancing insulin sensitivity and metabolic flexibility—and autophagy promotion, a cellular recycling process contributing to stress resistance, neuroprotection, and reduced inflammation [7,8]. These adaptations may favorably impact cardiometabolic and neurological health, suggesting IF as a non-pharmacological strategy for disease prevention and healthy aging [9,10]. TRE may provide additional benefits through circadian alignment, optimizing energy utilization and hormonal regulation [4]. IF may also influence gut microbiota, potentially counteracting age-related dysbiosis that contributes to chronic inflammation and frailty.
The aging population is expanding rapidly, with a high prevalence of cardiovascular disease, type 2 diabetes, and neurodegenerative disorders. Frailty, sarcopenia, and polypharmacy present unique challenges, increasing risks of drug–nutrient interactions that may affect dietary intervention safety and feasibility [11]. These physiological and clinical features necessitate age-specific IF evaluation, as older adults present metabolic and functional vulnerabilities that could benefit from—or be adversely affected by—fasting-induced changes.
Although numerous trials and reviews have established IF benefits in younger populations [12,13,14,15], evidence for older adults remains limited [16]. Existing studies often feature small samples, short follow-up, heterogeneous designs, and lack aging-specific subgroup analyses [2,17]. Furthermore, comparative effects of different IF protocols in older adults have not been synthesized. To address these gaps, we conducted a systematic review and network meta-analysis (NMA) to evaluate IF safety and effectiveness in adults aged ≥60 years, focusing on anthropometric, cardiometabolic, mental health, and cognitive outcomes.

2. Materials and Methods

2.1. Study Design

The present systematic review and NMA were conducted in accordance with the Cochrane handbook for systematic reviews of interventions [18]; in addition, the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) [19] and the PRISMA extension statement for conducting NMA were used to report the results [20]. The systematic review encompassed all eligible study designs to provide a comprehensive contextual synthesis of the available evidence, while the NMA was restricted exclusively to RCTs, in accordance with the methodological requirements of network meta-analysis and the assumptions of transitivity and consistency. This systematic review has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) [21] with the registration number CRD420251068135 (approved date 10 June 2025).

2.2. Data Sources and Search Strategy

A systematic search was performed in MEDLINE (PubMed), Scopus and ScienceDirect until June 2025, complemented by the manual screening of reference lists. The search combined MeSH terms and keywords for: population (adults ≥60 years: “older adults,” “elderly,” “aged”), interventions (IF modalities: “intermittent fasting,” “time-restricted eating,” “alternate-day fasting”), and outcomes (clinical variables, anthropometric measures, mental health and cognitive indicators). Searches were limited to English and Spanish publications without follow-up restrictions. Two researchers (SC and CS) independently conducted the search and screening, with discrepancies resolved by a third reviewer (II).
Studies were selected using PICOS criteria (Table 1). Exclusions comprised animal studies, those not reporting specified outcomes, and studies primarily in populations <60 years. Duplicates were removed manually in Excel, followed by title/abstract screening and full-text review with documented exclusion reasons. A PRISMA flow diagram was created to summarize the number of records identified, screened, assessed for eligibility and included (Figure 1). Multiple publications from the same cohort were treated as single studies, prioritizing the most comprehensive dataset.
Table 1. PICO elements used to define the research question.
Figure 1. PRISMA flow diagram.

2.3. Data Extraction

Two reviewers (SC and CS; 80% agreement) independently extracted data on study characteristics (author, year, country, design, sample size, and duration), participant features (age, sex, and health status), intervention details (IF type, control group, and fasting protocol), and outcomes (anthropometric, mental health, cognitive variables, dietary assessment, adjustments, and results). Discrepancies were resolved by consensus or a third reviewer (II).
For continuous outcomes, mean differences (MDs) and standard errors/deviations were extracted, prioritizing change from baseline over end-of-study values. Data were digitized from graphs when necessary, using WebPlotDigitizer. One eligible RCT used a crossover design; for this study, within-subject mean differences and standard errors from mixed-effects analyses were extracted, as recommended by the Cochrane Handbook for crossover trials.
Primary outcomes included body weight, depression, anxiety and cognitive function. Secondary outcomes encompassed anthropometric measures, glycemic and insulin markers, blood pressure, lipid profile, liver function, inflammatory markers and adverse events. Variables reported in <3 studies were excluded from NMA. Outcome units were standardized across studies.

2.4. Quality Assessment

Risk of bias was assessed using RoB 2.0 (RCTs) and ROBINS-I (non-randomized studies) by two independent reviewers (SC and CS), with disagreements resolved through discussion or adjudication. RoB 2.0 is the Cochrane tool for evaluating bias in randomized trials across domains such as randomization, deviations from intended interventions and outcome measurement, whereas ROBINS-I is the corresponding tool designed to assess bias in non-randomized studies by comparing them to a hypothetical target randomized trial. Detailed results of these assessments are presented in Supplementary Material S3.

2.5. Statistical Analysis

Analyses followed Cochrane [18] and NMA guidelines [20]. Seven studies were included. A frequentist NMA compared IF protocols (TRE, ADF, and 5:2) and controls for body weight and BMI; limited data precluded NMA for other outcomes. Sensitivity analyses restricted to RCTs and sequential exclusion identified outliers. Network geometry, league tables and P-scores evaluated comparative effectiveness. Consistency was assessed through global design-by-treatment approaches.
MD or SMD with 95% CI were calculated for continuous outcomes, using adjusted estimates when available, where MD represents absolute mean differences and SMD standardized mean differences across studies with different scales. Positive values indicated beneficial IF effects. Pairwise random-effects meta-analyses (DerSimonian–Laird) estimated direct comparisons between two interventions while accounting for between-study heterogeneity. Heterogeneity was quantified using Q (overall heterogeneity test), I2 (percentage of variability due to heterogeneity rather than chance) and τ2 (between-study variance), with prediction intervals used to assess the expected range of effects in future studies [22]. Treatment ranking used SUCRA values (0–1 scale, where higher values indicate higher probability of being among the best options) and mean ranks to summarize the comparative performance of each intervention across the network [23].
Sensitivity analyses excluded high-risk and non-randomized studies, and compared fixed versus random-effects models. Publication bias was explored with funnel plots (Supplementary Material S2: Figures S1 and S2); Egger’s test was not performed (<10 studies). Confidence in results was evaluated using the CINeMA framework [24] adapted from GRADE [25], assessing within-study bias, reporting bias, indirectness, imprecision, heterogeneity and incoherence.
Transitivity was assessed a priori by examining the distribution of potential clinical and methodological effect modifiers—including mean age, baseline body weight and BMI, proportion of participants with metabolic comorbidities, sex ratio, and intervention duration—across all pairwise treatment comparisons forming the network. Given that all NMA-eligible studies enrolled adults aged ≥60 years with comparable population characteristics and used usual diet or healthy living diet as comparators, the transitivity assumption was considered reasonably satisfied. Residual heterogeneity across studies was further addressed by retaining a random-effects model and is acknowledged in the certainty-of-evidence ratings. Analyses used R (version 4.5.1) with netmeta and metafor packages.

3. Results

3.1. Study Selection and Characteristics

Of the 31 studies meeting the inclusion criteria, 9 were RCTs [26,27,28,29,30,31,32,33,34], 12 were pre–post clinical trials without control groups [35,36,37,38,39,40,41,42,43,44,45,46], and 10 were observational cross-sectional or cohort studies [47,48,49,50,51,52,53,54,55,56]. Of these, only seven RCTs [26,27,28,29,30,33,34] satisfied the eligibility criteria for inclusion in the NMA. Pre–post and observational studies contributed exclusively to the narrative synthesis. Additionally, NMA was feasible only for body weight (Section 3.4.1) and BMI (Section 3.4.2), as insufficient data precluded network synthesis for other outcomes. Section 3.3 presents a structured narrative synthesis of findings from individual studies, organized by outcome domain. A PRISMA flow diagram was created with the Shiny app [57], which is an interactive web application created in R, to represent the screening process of articles found in the bibliographic search (Figure 1).
Sample sizes ranged from 9 to over 2.2 million participants. Most interventions tested TRE (TRE, typically 16:8 or 14:10), followed by 5:2 IF regimens and Ramadan fasting. Populations were heterogeneous, including healthy older adults, individuals with obesity, metabolic syndrome, cardiovascular risk, rheumatoid arthritis, chronic obstructive pulmonary disease, or mild cognitive impairment. The mean age across studies was above 60 years. Intervention durations varied between 4 and 12 weeks for clinical trials and up to 3 years for cohort studies. Studies were carried out in different countries, such as Poland [27,28], Malaysia [33,34,48,49], the USA [29,30,31,36,38,40,44,45,46], Spain [26,53,54], Iran [32], Tunisia [35,37,39,42,43], Australia [41], China [52,55,56], South Korea [50] and Italy [47,51]. Main characteristics and results are shown in Table 2, Table 3, Table 4, Table 5 and Table 6.
Table 2. Main characteristics of the included interventional studies.
Table 3. Main characteristics of the observational included studies.
Table 4. Main results of the included studies analyzing the association between IF, anthropometric data and physical health.
Table 5. Main results of the included studies analyzing the association between IF and mental health.
Table 6. Main results of the included studies analyzing the association between IF and cognitive health.

3.2. Risk of Bias and Study Quality

Risk of bias among RCTs ranged from low to moderate (Supplementary Material S3: Table S1). Four studies [26,30,31,32] were judged as low risk, whereas five others [27,28,29,33,34] were rated as having “some concerns,” primarily related to randomization procedures and selective reporting. Non-randomized studies generally showed fair to moderate quality on the NIH assessment tool, with higher quality observed in prospective cohorts [48,49,55,56] (Supplementary Material S4, Tables S2–S4). Sensitivity analyses restricting the NMA to RCTs only reduced heterogeneity and confirmed the overall direction of effects.

3.3. Results of the Systematic Review

3.3.1. Anthropometric and Body Composition Outcomes

Ten studies [27,28,30,33,34,38,40,41,45,48] evaluated IF effects on body weight, reporting reductions from −1.36 to −3.65 kg across different modalities (primarily TRE and IF 5:2).
TRE 16:8 studies showed consistent weight loss with muscle mass preservation. Short-term RCTs (6 weeks) in healthy older women [27] and overweight men [28] demonstrated weight loss of −1.36 kg and −1.50 kg, respectively, with BMI reductions of −1.29 and −0.50 kg/m2. The latter also showed a waist circumference reduction of −2.8 cm and decreased visceral fat without lean mass loss. A 4-week pre–post study in sedentary overweight adults [45] reported −2.15 ± 1.43 kg weight loss and −0.9 ± 0.6 kg/m2 BMI reduction with high adherence and minimal adverse events.
Longer-duration interventions showed more pronounced effects. A 12-week 14:10 TRE study in adults with metabolic syndrome [38] achieved −3.30 ± 3.20 kg weight loss, −1.09 ± 0.97 kg/m2 BMI reduction, and −4.46 cm waist circumference decrease with reductions in total and visceral fat. Another 12-week RCT comparing 8–10 h TRE to Mediterranean diet [30] showed −2.98 kg weight loss and −1.11 kg/m2 BMI reduction in the TRE group, significantly outperforming controls (−1.32 kg; p < 0.05), with decreased trunk fat and preserved lean mass.
The most notable finding comes from a 3-year prospective cohort [48]: older adults with mild cognitive impairment practicing regular ISF lost −3.65 kg with −1.53 kg/m2 BMI reduction and −3.57 cm waist circumference decrease, while non-fasters showed biomarker deterioration and weight-gain tendency.
IF 5:2 combined with caloric restriction also proved effective. Two 12-week studies in older men [33,34] using adapted ISF (two partial fasting days with 300–500 kcal plus five days of moderate restriction) reported weight losses of −2.80 kg and −2.5 kg with BMI reductions of −1.00 and −0.9 kg/m2, respectively, both with body fat percentage reductions.
Short-term interventions (4–8 weeks) demonstrated effectiveness even without controls: a 4-week TRE 16:8 study [40] showed −2.6 kg weight loss, while an 8-week study in older men with obesity [41] found −2.3 kg weight loss, −0.7 kg/m2 BMI reduction, and −4 cm waist circumference decrease with reduced visceral fat despite unchanged total caloric intake.

3.3.2. Metabolic and Cardiovascular Outcomes

Thirteen studies [26,29,30,31,32,33,38,41,48,49,53,55,56] evaluated IF effects on metabolic and cardiovascular variables, reporting heterogeneous but generally favorable results.
Glycemic control improved across multiple trials. A 12-week RCT [30] showed 8–10 h TRE reduced HbA1c by −0.12% versus the Mediterranean diet. An 8-week 14:10 TRE study [41] decreased fasting glucose (−0.3 mmol/L) and HbA1c (−0.2%) with improved postprandial glucose-dependent insulinotropic peptide responses. The 3-year ISF cohort [48] demonstrated −0.37 mmol/L fasting glucose reduction and marked insulin decrease (−16.25 pmol/L) in fasters versus metabolic deterioration in non-fasters. An 8-week 5:2 IF RCT [29] showed improvements in neuronal insulin resistance, with slightly greater effects in IF versus healthy-living diet.
Lipid profiles showed mixed results. The 12-week TRE trial in metabolic syndrome [38] significantly decreased total cholesterol (−13.16 mg/dL), LDL-c (−11.94 mg/dL), and non-HDL cholesterol (−11.63 mg/dL). However, a 6-week TRE 16:8 RCT in healthy adults [31] reported modest increases in total cholesterol (+11 mg/dL) and LDL-c (+11 mg/dL) without adverse clinical effects. Observationally, skipping dinner was associated with lower LDL-c and triglycerides versus skipping breakfast [50], while prolonged nightly fasting (≥12 h) was linked to reduced HDL-c (−2.79 mg/dL; p = 0.01) [53].
Blood pressure consistently improved. A 12-week metabolic syndrome TRE trial [38] reduced systolic (−5.12 mmHg) and diastolic pressure (−6.47 mmHg). TRE combined with the Mediterranean diet [26] achieved greater systolic reduction (−9.8 mmHg) versus diet alone (−13.3 mmHg in controls, with between-group differences favoring TRE for anthropometrics). A 12-week ISF + caloric restriction intervention [33] lowered systolic (−6.5 mmHg) and diastolic blood pressure (−2.2 mmHg). A 3-year cohort [48] showed −7.04 mmHg systolic blood pressure reduction in regular fasters versus no benefit in non-fasters.
Oxidative stress and inflammation markers improved notably. An 8-week TRE 16:8 RCT in postmenopausal women with rheumatoid arthritis [32] significantly reduced AST (−4.82 U/L), ALT (−2.34 U/L), MDA (−0.01 µM), and neutrophil-to-lymphocyte ratio (−0.11), while increasing catalase activity (+0.02 µM). A 3-year ISF cohort [48,49] reported MDA and C-reactive protein reductions with increased SOD activity in fasters—effects absent in non-fasters.
Arterial health and cardiovascular risk yielded complex results. A Chinese cross-sectional study [55] found that TRE with an eating window ≤11 h was associated with higher odds for arterial stiffness (OR = 1.70; 95% CI: 1.28–2.26), particularly in those at risk for malnutrition. Conversely, a U.S. NHANES prospective cohort [56] revealed a U-shaped relationship: night-time fasting >12.38 h was associated with 58% higher cardiovascular death risk (HR = 1.58; 95% CI: 1.10–2.28) versus intermediate durations (~11.5 h), which seemed to be the safest.

3.3.3. Mental Health Outcomes

Eight studies [34,35,36,43,46,51,52,54] examined IF effects on mental health in older adults, assessing mood, anxiety, depression, insomnia, and mental distress using validated instruments (POMS, GAD-7, GDS, and ISI).
Structured IF protocols improved mood and emotional well-being. A 12-week ISF + caloric restriction RCT [34] showed significant POMS reductions in tension (−1.0), anger (−1.9), and confusion (−2.0), with increased vigor (+1.6) and decreased total mood disturbance (−10.4).
Ramadan fasting produced mixed results. One pre–post study [43] found significant anxiety (GAD-7: −3) and depression (GDS: −1) reductions in both active and sedentary participants, but a similar 2022 study [35] found no significant changes despite physical performance improvements, suggesting physical activity’s moderating role.
Sleep quality varied by protocol. An 8-week 14:10 nightly TRE pilot study [36] in adults with memory decline reduced insomnia severity (ISI: −1.72), suggesting circadian-aligned eating windows may improve sleep. Conversely, Ramadan fasting worsened sleep quality in both active and sedentary groups [35].
Observational data revealed contrasting patterns. Italian older adults with ≤8 h eating windows had 86% lower mental distress odds (OR = 0.14; 95% CI: 0.03–0.65), independent of Mediterranean diet adherence and sociodemographic data [51]. However, a Spanish cohort showed that those fasting ≥12 h overnight had significantly higher clinical depression prevalence versus ≤9 h fasters, even after adjusting for confounders [54].
Two studies found no significant effects: a 4-week TRE intervention [46] reported high satisfaction, but no measurable mood changes, and a Chinese cross-sectional study [52] found no association between 14:10 TRE and depression or sleep duration.

3.3.4. Cognitive Outcomes

Fourteen studies [28,29,31,35,36,37,39,43,45,46,47,48,49,52] examined IF effects on cognition. Across included studies, cognitive function was operationalized using a range of validated standardized neuropsychological instruments: MMSE, MoCA, RAVLT, MAPS, reaction time measures and the NIH Toolbox Cognition Battery. These instruments assess distinct cognitive domains, including global status (MMSE and MoCA), episodic memory (RAVLT), processing speed (Digit Symbol test) and executive function. None of the included studies used clinically diagnosed dementia incidence as an outcome; all cognitive findings reflect measurable changes in test performance. Benefits emerged primarily in structured, long-term, or circadian-aligned protocols, while short-term or disruptive fasting showed mixed results.
Structured, circadian-aligned IF consistently improved cognition. An 8-week 5:2 IF RCT [29] significantly enhanced executive function, fluency, set-shifting, cued recall, and global performance, reducing “brain age” by 2.63 years versus healthy-living diet controls. An 8-week nightly 14:10 TRE pilot [36] (eating window ending by 8 PM) improved global cognitive function (+11.88 MAPS points) in adults with memory decline. Cross-sectional Italian data [47] showed TRE practitioners (≤10 h window) had 72% lower cognitive impairment odds (OR = 0.28; 95% CI: 0.07–0.90), particularly with breakfast inclusion.
Long-term regular fasting yielded the most robust benefits. The 3-year prospective cohort [48] in adults with mild cognitive impairment showed significant improvements across all domains in regular ISF practitioners: MMSE (+6.43), MoCA (+5.16), RAVLT (+6.05), and processing speed (+1.28 Digit Symbol), while non-fasters declined markedly. Follow-up analysis [49] confirmed regular fasters scored significantly higher than non-fasters on MMSE (24.05 vs. 16.33), MoCA (19.43 vs. 14.37), and memory tests.
Ramadan IF produced activity-dependent outcomes. Physically active participants showed improved executive function, attention, inhibition, memory [35], and reduced vigilance reaction time [43]. However, sedentary participants experienced declined associative learning [35], and both groups showed worsened simple reaction time during weeks 2 and 4 [37,39].
Short-term or unstructured TRE generally showed no effects. A 4-week TRE 16:8 intervention [45] and two 6-week RCTs [28,31] found no MoCA or MMSE changes in sedentary overweight adults, healthy women, and overweight men, respectively. A 4-week feasibility study [46] also reported no cognitive changes.
Notably, very short eating windows were associated with worse performance. In a Chinese cohort [52], older adults consuming all calories within ≤10 h had significantly lower MMSE scores (22.45 vs. 24.97; p < 0.001), particularly in orientation and attention/calculation domains.

3.4. Results of the Network Meta-Analysis

3.4.1. Body Weight (kg)

A network meta-analysis (NMA) including seven randomized studies compared six dietary interventions (HLD, IF 5:2, ISF, TRE 12:12, TRE 16:8, and usual diet [UD] as reference) for body weight reduction. In Figure 2, we present the network geometry plot, which is a graphical map of the network meta-analysis showing each intervention as a node and the available direct comparisons between interventions as connecting lines, with line thickness reflecting the amount of evidence. All seven studies included in the NMA were RCTs, ensuring that the pooled estimates and treatment rankings are derived exclusively from experimental, randomized evidence.
Figure 2. Network geometry plot.
No evidence of heterogeneity was observed across the network (Total Q = 0.26, df = 2, p = 0.88). Heterogeneity within designs was also negligible (Q = 0.26, df = 2, p = 0.88), indicating that results were highly consistent among studies comparing the same interventions. Design-specific analyses confirmed the absence of heterogeneity for the direct comparisons: ISF vs. UD (Q = 0.26, p = 0.61) and TRE 16:8 vs. UD (Q = 0.00, p = 0.99).
Assessment of global inconsistency through design-by-treatment interaction could not be performed due to the absence of closed loops in the network, which is expected in networks with a star-shaped structure. Finally, tau2 was estimated as 0, further supporting the extreme homogeneity among studies.
The pooled effect estimate indicated a significant overall reduction in body weight (MD = −2.04 kg; SE = 0.22; 95% CI −2.47 to −1.61; p < 0.001). Given the absence of between-study heterogeneity, the prediction interval was narrow and overlapped the confidence interval (−2.61 to −1.47). A random-effects model was retained to account for potential clinical and methodological variability, in accordance with PRISMA-NMA recommendations.
Using UD as the reference, ISF and TRE 16:8 demonstrated statistically significant weight reductions with precise estimates (ISF: MD = −2.36 kg, 95% CI −2.93 to −1.79; TRE 16:8: MD = −1.92 kg, 95% CI −2.57 to −1.27; both p < 0.0001). In contrast, IF 5:2, HLD, and TRE 12:12 showed no clear evidence of benefit over UD, as confidence intervals crossed the null effect (Table 7). In this network of seven studies, rankings were inherently unstable and should be interpreted with caution; small changes in the included evidence could substantially alter ranking order.
Table 7. Estimated effects of dietary interventions compared with the UD on weight loss.
Figure 3 presents all pairwise mean differences (95% CIs) for weight for every treatment comparison within the network, including both direct and indirect estimates, with certainty ratings per comparison. In the color scale, blue cells indicate comparatively more beneficial effects (greater weight reduction relative to the reference treatment), whereas red cells indicate comparatively less beneficial or unfavorable effects.
Figure 3. League table of pairwise comparisons for weight outcomes.
Ranking probabilities based on P-scores identified ISF as the most effective intervention (0.850), followed by IF 5:2 (0.704) and TRE 16:8 (0.667). TRE 12:12 (0.471) and HLD (0.182) ranked lower, while UD showed the lowest probability of effectiveness (0.126). These rankings should be interpreted alongside effect sizes and certainty of evidence (Table 8).
Table 8. P-score rankings for weight loss and BMI reduction across interventions.
Clinical imprecision was assessed using a prespecified threshold of ±3.5 kg (5% of a reference body weight of 70 kg) [58,59], consistent with clinically meaningful weight loss. Two studies presented serious imprecision, with confidence intervals crossing this threshold [26,29], whereas the remaining studies showed low imprecision [27,28,30,33,34], supporting the clinical relevance of the observed effects.
All included studies contributed direct evidence to their respective comparisons, and no study relied solely on indirect evidence. Although some treatment contrasts were informed only indirectly at the network level, concerns regarding indirectness were considered minor and did not affect the certainty of evidence for individual comparisons. Visual inspection of funnel plots revealed no clear asymmetry, suggesting a low risk of publication bias (Supplementary Material S2).

3.4.2. BMI (kg/m2)

The network meta-analysis compared six dietary interventions (HLD, IF 5:2, ISF, TRE 12:12, TRE 16:8, and usual diet [UD] as reference). All seven studies included in the NMA were RCTs, ensuring that the pooled estimates and treatment rankings are derived exclusively from experimental, randomized evidence.
The network showed evidence of heterogeneity (Total Q = 6.95, df = 2, p = 0.031), indicating some variability among the included studies. Heterogeneity within designs was similar (Q = 6.95, df = 2, p = 0.031). Design-specific analyses indicated that heterogeneity was present for TRE 16:8 vs. UD (Q = 6.48, p = 0.011), while ISF vs. UD showed no evidence of heterogeneity (Q = 0.47, p = 0.49).
Global inconsistency could not be assessed due to the absence of closed loops in the network. Estimated tau within designs was 0.3981, and tau2 within designs was 0.1585, reflecting moderate heterogeneity among studies.
The pooled random-effects estimate showed a statistically significant reduction in BMI (MD = −0.77 kg/m2; SE = 0.09; z = −8.48; p < 0.001), with a narrow 95% confidence interval (−0.95 to −0.59) and a nearly identical prediction interval (−0.97 to −0.57), reflecting substantial homogeneity of effects.
P-score ranking placed TRE 16:8 as the most effective intervention (0.751), followed by IF 5:2 (0.729) and ISF (0.618). TRE 12:12 (0.499) and HLD (0.259) showed lower probabilities of benefit, while UD ranked lowest (0.143). Notably, IF 5:2 achieved a relatively high ranking despite lacking statistical significance versus UD (Table 8).
Using UD as the comparator, TRE 16:8 and ISF demonstrated statistically significant BMI reductions (TRE 16:8: MD = −1.01 kg/m2, 95% CI −1.69 to −0.33, p = 0.0037; ISF: MD = −0.81 kg/m2, 95% CI −1.43 to −0.19, p = 0.0106). IF 5:2, HLD, and TRE 12:12 did not differ significantly from UD, as their confidence intervals crossed the null effect (Table 9). Figure 4 presents all pairwise mean differences (95% CIs) for BMI for every treatment comparison within the network, including both direct and indirect estimates, with certainty ratings per comparison.
Table 9. Estimated effects of dietary interventions compared with the UD on BMI loss.
Figure 4. League table of pairwise comparisons for BMI outcomes.
Clinical imprecision was evaluated using a prespecified threshold of ±1.25 kg/m2, corresponding to a 5% weight loss for a reference individual (70 kg, 1.70 m) [58,59]. Five studies [26,27,28,29,30] exhibited serious imprecision, with confidence intervals crossing this threshold, whereas two studies [33,34] showed moderate imprecision, with lower bounds close to the cutoff.
All included studies contributed direct evidence through pairwise comparisons, and no trial relied exclusively on indirect evidence. Although some treatment contrasts were informed only indirectly at the network level, concerns regarding indirectness were considered minor and did not affect individual study certainty. Funnel plot inspection suggested possible publication bias driven by one small study [27], which appeared as an outlier with a high standard error (Supplementary Material S2).

4. Discussion

This systematic review and NMA evaluated the safety and effectiveness of IF in adults aged ≥60 years. Our findings suggest that IF is generally feasible and appears to have an acceptable short-term safety profile in older adults, with modest but clinically meaningful benefits. ISF and TRE 16:8 showed the strongest comparative effects for body weight reduction (MD: −2.36 kg and −1.92 kg, respectively) and BMI reduction in the RCT-based NMA. Preservation of lean muscle mass was consistently reported across the included studies evaluating these protocols in the systematic review. Improvements were also observed in HbA1c, systolic blood pressure, and LDL cholesterol. However, evidence regarding mental health and cognitive outcomes remains inconclusive and highly heterogeneous.
The quantitative scope of the NMA is limited to body weight and BMI, for which sufficient RCT data were available. All other outcomes discussed in this review reflect narrative synthesis and must not be interpreted as comparative network estimates.

4.1. Anthropometric and Body Composition Outcomes

Weight loss documented across our studies (−1.36 to −3.65 kg) aligns closely with meta-analyses in mixed populations [60,61,62,63], suggesting IF’s mechanisms extend beyond age barriers. Our results parallel Semnani-Azad et al.’s findings (−3.40 kg for ADF, −1.72 kg for TRE) [62] and Chen et al.’s data in women (−1.927 kg) [61], indicating comparable responses across age groups.
It seems that intervention duration is critical: our 3-year prospective study [48] documenting −3.65 kg represents one of the longest follow-ups in geriatric literature, with interventions ≥24 weeks showing more sustained effects [62]. TRE 16:8 consistently demonstrated high adherence rates (>80%) with minimal adverse events, whereas more restrictive protocols showed greater variability [64,65,66,67].
Systematic preservation of muscle mass in TRE studies holds particular relevance given the risk for sarcopenia in older adults [68,69]. TRE 16:8 studies consistently reported the absence of lean mass loss [27,28,30], contrasting favorably with traditional continuous caloric restriction [70]. An umbrella review documented significant increases in fat-free mass (MD = 0.98 kg; 95% CI: 0.18–1.78) [63], likely reflecting preferential adipose tissue reduction.
Reductions in waist circumference (−2.8 to −4.46 cm) exceed clinically significant thresholds for cardiometabolic risk reduction [71], with effects particularly pronounced in combined 5:2 ISF protocols. The preferential loss of visceral fat—more metabolically active and proinflammatory—carries important metabolic implications in older adults [72,73].
Effects were more pronounced in populations with metabolic syndrome than in healthy individuals [74,75], suggesting specific therapeutic potential in those with geriatric comorbidities. These patterns imply complex metabolic adaptations, including improvements in insulin sensitivity and optimization of circadian rhythms related to lipid metabolism [76,77,78,79,80,81].

4.2. Metabolic and Cardiovascular Outcomes

Glycemic improvements with TRE, particularly HbA1c reductions, are comparable to meta-analyses in younger populations and fall within clinically relevant ranges for type 2 diabetes prevention [82,83,84,85]. TRE emerged as the most effective modality for fasting glucose reduction [62,83,86,87], likely through improvements in insulin sensitivity and pancreatic function optimization.
Lipid profile effects showed greater variability, with some trials documenting improvements in cholesterol and LDL-c while others reported modest increases in short TRE studies [75]. Blood pressure reductions were more consistent (−5.12 to −13.3 mmHg systolic) across different modalities [88,89].
Reductions in inflammatory markers (MDA, CRP, neutrophil–lymphocyte ratio) with increases in catalase and superoxide dismutase suggest robust anti-inflammatory effects. A network meta-analysis documented significant reductions in TNF-α (SMD: −0.31), CRP (SMD: −0.19), and leptin (SMD: −0.57) [90]. TRE appeared to cause the greatest TNF-α reductions (−0.39), particularly relevant given chronic low-grade inflammation’s role in functional decline and age-related diseases [91].
Concerning findings emerged from observational studies: nocturnal fasting >12.38 h was associated with a 58% higher cardiovascular mortality, while eating windows ≤11 h were linked to greater arterial stiffness. Taken together, these patterns are consistent with the possibility of a non-linear (U-shaped) relationship between fasting duration and cardiovascular outcomes, in which intermediate fasting intervals (around 11.5 h) may be comparatively safer, but this remains speculative. Mechanisms may involve adverse effects on heart rate variability, autonomic function, or medication interactions. However, these findings (e.g., cardiovascular mortality risk with prolonged nocturnal fasting, HR = 1.58; 95% CI: 1.10–2.28) derive exclusively from observational studies and are subject to inherent limitations, including residual and unmeasured confounding. Accordingly, these associations should be regarded as hypothesis-generating and interpreted with great caution, rather than as evidence of a causal effect.

4.3. Mental Health and Cognitive Outcomes

Mental health results reveal marked dependence on protocol structure. Circadian rhythm-aligned protocols (nocturnal TRE 14:10 or regular ISF) showed consistent benefits in mood, anxiety, and depression. Conversely, observational studies documented 86% lower mental distress in eating windows ≤8 h [51] but higher depression prevalence with nocturnal fasts ≥12 h [92], underscoring the importance of circadian alignment.
Cognitive effects present a complex pattern. Long-duration structured protocols showed robust benefits, particularly our 3-year study documenting improvements across all dimensions (MMSE +6.43, MoCA +5.16, RAVLT +6.05). However, a non-linear relationship emerged: while 8–10 h windows associated with better function, windows ≤10 h paradoxically linked to lower MMSE scores [52]. Ramadan studies suggest physical activity significantly modulates cognitive effects [35].

4.4. Clinical Implications for Older Adults

Mechanisms underlying observed effects involve metabolic flexibility through switching between substrate utilization [93], particularly relevant given age-related metabolic decline. Anti-inflammatory effects may additionally mitigate inflammaging [91].
Clinical implementation requires careful individualization. Initial protocols should be less restrictive (14:10 or 16:8), allowing gradual adaptation. Extremely restrictive windows (<8 h) should be avoided, given cardiovascular risk evidence. Circadian alignment should be prioritized over extreme restriction.
Integration with geriatric considerations is essential: adequate protein intake to prevent sarcopenia, monitoring of medication interactions, consideration of social eating aspects, and screening for malnutrition risk. Specific risks include dehydration, orthostatic hypotension, electrolyte disturbances, hypoglycemia in diabetics, and side effects that potentially increase fall risk.

4.5. Limitations and Future Directions

Most RCTs lasted <24 weeks, limiting conclusions about long-term sustainability. Publication bias may inflate effectiveness estimates. We could not assess IF interactions with medications, particularly relevant in this population.
Intervention heterogeneity within network nodes represents a relevant source of uncertainty. As the evidence base expands, future NMAs should disaggregate IF protocols with greater granularity, distinguishing protocols by fasting duration, eating window timing, caloric restriction depth, and circadian alignment.
In the context of Islamic Sunnah fasting, spiritual and faith-based practices (e.g., communal worship, structured routines, stress reduction, and sense of purpose) may also contribute to health benefits, independently of or alongside metabolic effects of IF. However, the included ISF studies did not assess religiosity or spiritual well-being, so these influences could not be disentangled. Future research on religious fasting should incorporate such measures to clarify their role.
Future research should prioritize longer-duration trials with longitudinal muscle mass evaluations through advanced imaging, sarcopenia biomarkers, functional outcomes, and systematic adverse event monitoring. Studies examining IF interactions with lifestyle modifiers are needed.

5. Conclusions

This systematic review and network meta-analysis evaluated IF protocols in adults aged ≥60 years. Moderate-certainty evidence from seven RCTs suggests that TRE 16:8 and ISF produce statistically significant and clinically meaningful reductions in body weight (ISF: −2.36 kg, 95% CI −2.93 to −1.79; TRE 16:8: −1.92 kg, 95% CI −2.57 to −1.27) and BMI compared to usual diet, with minimal heterogeneity in the networks (weight: Q = 0.26, p = 0.88; BMI: Q = 6.95, p = 0.03).
The systematic review suggests these protocols are associated with improvements in metabolic markers (HbA1c and blood pressure) and preservation of lean muscle mass across included studies, though comparative quantitative evidence is limited to anthropometric outcomes. Mental health and cognitive findings derive exclusively from narrative synthesis of heterogeneous study designs and remain exploratory.
Future trials should be long-term, statistically well-powered, and age-specific, directly comparing protocols while accounting for modulators such as frailty, comorbidities, circadian phenotype, and polypharmacy. Personalization of IF regimens and evaluation of long-term safety are essential to develop evidence-based dietary strategies for healthy aging.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/nu18091450/s1, Supplementary Material S1: Search strategy; Supplementary Material S2: Figure S1: Funnel plot for assessment of publication bias in network meta-analysis of intermittent fasting interventions for weight loss; Figure S2: Funnel plot for assessment of publication bias in network meta-analysis of intermittent fasting interventions for BMI loss; Supplementary Material S3: Table S1: Assessment of risk of bias in randomized trials (RoB 2); Supplementary Material S4: Table S2: Quality assessment of controlled intervention studies; Table S3: Quality assessment tool for observational cohort and cross-sectional studies; Table S4: Quality assessment tool for before–after (pre–post) studies with no control group.

Author Contributions

Conceptualization: S.C.-A. and I.I.; Data curation: S.C.-A. and C.M.S.-P.; Formal analysis: S.C.-A.; Investigation: S.C.-A. and I.I.; Methodology: S.C.-A., I.I. and M.C.C.; Project administration: S.C.-A.; Resources: S.C.-A.; Software: S.C.-A.; Supervision: I.I. and M.C.C.; Validation: I.I. and M.C.C.; Visualization: S.C.-A.; Writing—original draft: S.C.-A.; Writing—review and editing: I.I. and M.C.C. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Ethical review and approval were waived for this study due to the nature of the article type (systematic review).

Data Availability Statement

All data generated or analyzed during this study are included in this published article and its Supplementary Material.

Acknowledgments

During the preparation of this manuscript, the authors used Claude Sonnet 4.5 for the purposes of improving the fluency and readability of the existing text, and Gemini 3 for creating the graphical abstract. The authors have reviewed and edited the output and take full responsibility for the content of this publication.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

IFIntermittent fasting
TRETime-restricted eating
ISFIslamic Sunnah fasting
NMANetwork meta-analysis
RCTsRandomized controlled trials
ADFAlternate-day fasting
BMIBody mass index
HbA1cHemoglobin A1c
LDLLow-density lipoprotein
MMSEMini-Mental State Examination
MoCAMontreal Cognitive Assessment
RAVLTRey Auditory Verbal Learning Test
MAPSMemory and Aging Performance Scale
NIHNational Institutes of Health
PICOSPopulation, Intervention, Comparison, Outcomes, Study design
PRISMAPreferred Reporting Items for Systematic Reviews and Meta-Analyses
PROSPEROInternational Prospective Register of Systematic Reviews
MDMean difference
RoB 2.0Risk of Bias 2.0
ROBINS-IRisk Of Bias In Non-randomized Studies of Interventions
SUCRASurface Under the Cumulative Ranking curve
CINeMAConfidence In Network Meta-Analysis
CIConfidence interval
HLDHealthy living diet
UDUsual diet
GDSGeriatric Depression Scale
POMSProfile of Mood States
GAD-7Generalized Anxiety Disorder-7
ISIInsomnia Severity Index
OROdds ratio
ASTAspartate aminotransferase
ALTAlanine aminotransferase
MDAMalondialdehyde
SODSuperoxide dismutase

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