What randomized controlled trials exist comparing intermittent fasting to standard calorie-restricted diets for long-term weight maintenance?
Executive summary
Randomized controlled trials (RCTs) directly comparing intermittent fasting (IF) to continuous/daily caloric restriction (CCR or DCR) exist but are relatively few, often short-to-moderate in duration, and produce mixed results: most pooled analyses find no large long‑term advantage of IF over standard calorie‑restriction for weight maintenance, though some individual 12‑month trials report modest benefits for particular IF schedules (4:3 / 5:2 / ADF) and mixed signals on insulin sensitivity [1] [2] [3] [4].
1. What trials actually randomized people to IF vs daily calorie restriction and followed them long enough to assess maintenance
Several RCTs extended to ~50–52 weeks and therefore speak most directly to “long‑term” maintenance: Schübel et al. ran a 50‑week randomized trial comparing intermittent and continuous calorie restriction (specifically examining weight and metabolism over 50 weeks) and is highlighted in multiple meta‑analyses as one of the longest RCTs available [5] [6]. A 52‑week trial protocol called DRIFT was designed to randomize adults to DCR versus an IMF regimen with equivalent weekly energy deficits and explicitly target 52‑week weight maintenance outcomes (protocol published; trial ongoing/registered) [7]. An Int J Obes publication from 2019 reporting a 12‑month comparison of intermittent versus continuous restriction is repeatedly cited in reviews as a principal long‑duration RCT [7]. More recent single‑site reports—such as the University of Colorado group’s one‑year 4:3 intermittent fasting trial—reported greater weight loss for IMF vs DCR at one year in that study (7.6% vs 5% weight loss) but require scrutiny for design, intensity of behavioral support, and generalizability [8].
2. What the pooled evidence says about long‑term maintenance
Systematic reviews and meta‑analyses that pooled RCTs up through late 2022–2023 generally conclude that IF and continuous energy restriction produce similar weight outcomes over the long term: a 2025 systematic review identified 16 RCTs (n≈1,258) through Sept 2023 and reported no clear superiority of IF for long‑term weight outcomes, although some short‑term cardiometabolic signals (e.g., insulin sensitivity) appeared [1]. Another 2024 review concluded FBS (fasting‑based strategies) did not show superior long‑term outcomes to CCR despite short‑term insulin benefits [2]. Large network meta‑analyses that included trials up to 52 weeks find that any small advantages of particular IF patterns (alternate‑day fasting or 4:3/5:2) tend to attenuate in longer trials, and overall effectiveness depends more on total energy restriction than the timing pattern [4] [9].
3. Notable single trials that influenced conclusions
The Schübel 50‑week randomized trial is frequently cited as evidence that differences narrow with time [5] [6]. The 12‑month Int J Obes trial and the University of Colorado 4:3 one‑year report stand out because they either directly tested weight maintenance or reported 12‑month outcomes: the CU Anschutz study observed a modestly larger percentage weight loss at one year in the IMF arm (7.6% vs 5%) but the intervention included intensive support (weekly group sessions early on), which may explain part of the effect beyond the fasting schedule itself [8] [7]. Reviews flag that two RCTs showed improved insulin sensitivity with certain IF patterns (4:3 and 5:2) compared with DCR, but the evidence is limited and not consistent across trials [3].
4. Limitations, heterogeneity, and hidden agendas in the literature
The RCT evidence base is heterogeneous: trials use different IF variants (ADF, TRE, 5:2, 4:3), different control diets, variable caloric matching (isocaloric vs ad‑libitum), and differing behavioral supports and adherence measures, which complicates head‑to‑head inference [10] [5]. Meta‑analyses note short trial durations for many studies (average ~12 weeks in some reviews), variable risk of bias, and loss of any early advantages by longer follow‑up; industry or advocacy enthusiasm for IF can overemphasize single positive trials without acknowledging that many pooled estimates show parity with CCR [4] [11]. Where claims of “superiority” appear, detailed methods often reveal differing intensity of counseling or caloric goals that confound attribution to the fasting pattern alone [8] [1].
5. Bottom line for the question posed
RCTs comparing IF to standard calorie restriction do exist, including several that reach ~50–52 weeks (Schübel et al., Int J Obes 12‑month trials, the DRIFT protocol and the CU Anschutz 1‑year report), but pooled evidence from systematic reviews and network meta‑analyses finds little consistent long‑term weight‑maintenance advantage of IF versus continuous calorie restriction; some IF schedules may yield modest additional benefits for weight or insulin sensitivity in specific trials, but heterogeneity and differences in non‑dietary supports limit simple conclusions [5] [7] [1] [4].