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Meal A Day and Antro
Meal A Day and Antro
Meal A Day and Antro
Clinical Center of the University of Pécs, Medical School, University of Pécs, Pécs, Hungary; 3 Institute for Biomedicine of Aging, Friedrich-Alexander-Universität
Erlangen-Nürnberg, Nürnberg, Germany; 4 Institute for Biometrics and Epidemiology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research at
Heinrich Heine University Düsseldorf, Düsseldorf, Germany; and 5 Cochrane Germany, Cochrane Germany Foundation, Freiburg, Germany
ABSTRACT
The relation between meal frequency and measures of obesity is inconclusive. Therefore, this systematic review and network meta-analysis (NMA)
set out to compare the isocaloric effects of different meal frequencies on anthropometric outcomes and energy intake (EI). A systematic literature
search was conducted in 3 electronic databases (Medline, Cochrane Library, Web of Science; search date, 11 March 2019). Randomized controlled
trials (RCTs) were included with ≥2 wk intervention duration comparing any 2 of the eligible isocaloric meal frequencies (i.e., 1 to ≥8 meals/d).
Random-effects NMA was performed for 4 outcomes [body weight (BW), waist circumference (WC), fat mass (FM), and EI], and surface under the
cumulative ranking curve (SUCRA) was estimated using a frequentist approach (P-score: value is between 0 and 1). Twenty-two RCTs with 647
participants were included. Our results suggest that 2 meals/d probably slightly reduces BW compared with 3 meals/d [mean difference (MD):
−1.02 kg; 95% CI: −1.70, −0.35 kg) or 6 meals/d (MD: −1.29 kg; 95% CI: −1.74, −0.84 kg; moderate certainty of evidence). We are uncertain whether
1 or 2 meals/d reduces BW compared with ≥8 meals/d (MD1 meal/d vs. ≥8 meals/d : −2.25 kg; 95% CI: −5.13, 0.63 kg; MD2 meals/d vs. ≥8 meals/d : −1.32 kg;
95% CI: −2.19, −0.45 kg) and whether 1 meal/d probably reduces FM compared with 3 meals/d (MD: −1.84 kg; 95% CI: −3.72, 0.05 kg; very low
certainty of evidence). Two meals per day compared with 6 meals/d probably reduce WC (MD: −3.77 cm; 95% CI: −4.68, −2.86 cm; moderate
certainty of evidence). One meal per day was ranked as the best frequency for reducing BW (P-score: 0.81), followed by 2 meals/d (P-score: 0.74),
whereas 2 meals/d performed best for WC (P-score: 0.96). EI was not affected by meal frequency. In conclusion, our findings indicate that there is
little robust evidence that reducing meal frequency is beneficial. Adv Nutr 2020;11:1108–1122.
1108 Copyright
C The Author(s) on behalf of the American Society for Nutrition 2020. Adv Nutr 2020;11:1108–1122; doi: https://doi.org/10.1093/advances/nmaa056.
suggested that lowering meal frequency through skipping i) If the amount of energy intake was exchanged with an
breakfast and thereby prolonging fasting times may help to equal amount of energy intake for the different meal
reduce weight in adults (7). frequency interventions within a trial.
Given these contradictions, it is also still unclear whether a) Hypo vs. hypocaloric energy intake within a trial
an increased meal frequency through snacking between b) Eucaloric vs. eucaloric energy intake within a trial
main meals influences anthropometric outcomes. Generally, ii) If the RCT involved overfeeding, such that excess
there are healthy (e.g., fruit, salads, or nuts) and unhealthy energy was supplied, resulting in a positive energy
(e.g., sweets or crisps) snacks that have a different effect balance, then the comparison was still considered
on health and anthropometric outcomes as well (1). Yet, isocaloric as long as the comparator was matched for
no consensus on the relation between meal frequency—by the excess energy, resulting in the same positive energy
spreading main meals over more eating occasions or through balance.
healthy snacking—and obesity has been reached (8). a) Hyper vs. hypercaloric energy intake within a trial
Compared with the above-described pairwise meta- 3) Minimum duration of the intervention: ≥2 wk, in line
analyses, the methodological approach of network meta- with a recent meta-analysis on breakfast skipping (7).
analysis (NMA) offers the possibility to combine direct 4) Participants with a mean age ≥18 y.
(i.e., from trials comparing 2 meal frequency interventions
directly: e.g., 3 meals/d vs. 6 meals/d) and indirect (i.e., The following studies were excluded:
from a connected root via ≥1 intermediate comparators) 1) RCTs of acute (single meal) postprandial effects only.
evidence in a network of trials. To the best of our knowledge, 2) RCTs with critically ill and hospitalized patients, patients
no NMA has been conducted to date that simultaneously undergoing bariatric surgery, patients with eating disor-
compared the isocaloric effects of different meal frequencies ders.
on anthropometric outcomes and energy intake. Therefore, 3) RCTs based solely on liquid/formula diets, meal replace-
the aim of the present research project was to investigate the ment interventions, or dietary supplements.
impact of different meal frequencies, combine the direct and 4) Co-intervention (e.g., drugs, supplements, diet, or physi-
indirect evidence, and rank the different dietary approaches cal activity) not applied in all intervention arms.
for effects on anthropometric outcomes (body weight, waist
circumference, fat mass) and energy intake using NMA
methodology. Data extraction
For included studies, 2 reviewers independently (KB, JZ)
extracted the following characteristics to a piloted data
Methods
extraction form: name of first author, year of publica-
This NMA was registered in PROSPERO (International
tion, study origin (country), study design (RCT: paral-
Prospective Register of Systematic Reviews; www.crd.york.
lel or crossover, including duration of washout period),
ac.uk/prospero/index.asp, identifier CRD42019138572) and
comparison of meal frequency type, sample size, disease
is being reported in adherence to PRISMA (Preferred
status (i.e., healthy, obese, type 2 diabetic, hypercholes-
Reporting Items for Systematic Reviews and Meta-Analyses)
terolemia), mean age, mean BMI, presence of type 2
standards for reporting NMAs (9, 10).
diabetes (T2D; %), gender, duration of intervention (weeks),
specification of the type of isocaloric comparison within
Search strategy an RCT (i.e., hypocaloric, eucaloric, hypercaloric), provi-
The systematic literature search was performed in the sion of food (yes/no), meals consumed in research center
electronic databases Medline (Supplemental Appendix 1), (yes/no), energy intake and macronutrient composition,
Web of Science, and the Cochrane Central Register of outcomes extracted for the present NMA, and dietary
Controlled Trials (CENTRAL) up until 11 March 2019, with adherence.
no restriction of language and calendar date. Furthermore, The preferred outcome data were change scores adjusted
the reference lists from eligible studies were screened for baseline measurements with corresponding SDs, followed
to identify additional relevant research. Screening and by postintervention values and change scores not adjusted for
study selection were conducted by 2 authors independently baseline measurements, as reported previously (12).
(LS, KB).
Risk-of-bias assessment
Selection of studies Risk of bias (RoB) was assessed by 2 authors indepen-
Studies were included in the NMA if they met the following dently (SL, GT) according to the methods described in the
criteria: Cochrane Handbook for Systematic Reviews of Interventions
(13). The following domains were considered: selection bias
1) RCTs (with a parallel or crossover design) examining (random-sequence generation and allocation concealment),
≥2 dietary meal frequency interventions per day: 1 performance bias (blinding of participants and personnel),
meal/d vs. 2 vs. 3 vs. 4 vs. 5 vs. 6 vs. 7 vs. ≥8. detection bias (blinding of outcome assessment), attrition
2) Isocaloric comparison (11): bias (incomplete outcome data), reporting bias (selective
n n
n
n n
n
n
n
n
Schwingshackl et al.
Author, year, reference (country) or crossover) length, wk (length) frequency size, n status Mean age, y kg/m2 T2D, % Female, %
Alencar et al., 2015 (23) USA RCT, crossover 2 2 wk 6 vs. 2 11 Obesity 52 39.1 0 100
Antoine et al., 1984 (24) France RCT, crossover 2 None 6 vs. 3 10 Obesity 40.9 31.8 NR 100
Arciero et al., 2013 (25) USA RCT, parallel 4 — 6 vs. 3 30 Overweight or obesity 46 29.9 0 86
Arnold et al., 1993 (26) New Zealand RCT, crossover 2 1–7 d 9 vs. 3 19 Healthy 32.1 23.1 0 50
Arnold et al., 1994 (27) New Zealand RCT, crossover 4 None 9 vs. 3 16 Hypercholesterolemia 49.9 26.5 0 31
Arnold et al., 1997 (28) New Zealand RCT, crossover 4 None 9 vs. 3 13 T2D, impaired glucose 46–70 (range) 29.9 85 69
tolerance
Bachman and Raynor, USA RCT, parallel 24 — 7–9 vs. 3 51 Overweight or obesity 51 35.5 0 58
2012 (29)
Berteus Forslund et al., Sweden RCT, parallel 52 — 6 vs. 3 140 Obesity 39.5 38.4 0 74
2008 (30)
Cameron et al., 2010 (31) Canada RCT, parallel 8 — 6 vs. 3 18 Obesity 35.5 36 0 50
Finkelstein and Fryer, USA RCT, parallel 9 — 6 vs. 3 8 Overweight 20–22 26.9 0 100
1971 (32)
Iwao et al., 1996 (33) Japan RCT, parallel 2 — 6 vs. 2 12 Healthy 20 20.9 0 NR
Jenkins et al., 1995 (34) Canada RCT, crossover 2 3 wk 17 vs. 3 7 Normal weight and 39.6 NR 0 0
overweight
Kahleova et al., 2014 (35) Czech Republic RCT, crossover 12 None 6 vs. 2 54 T2D 59.4 32.6 100 46
Koopman et al., 2014 (36) Netherlands RCT, parallel 6 — 6 vs. 3 36 Healthy 22 22.5 0 0
Murphy et al., 1996 (37) UK RCT, crossover 2 3 wk 12 vs. 2 11 Healthy 22 23.6 0 100
Papakonstantinou et al., Greece RCT, crossover 12 None 6 vs. 3 45 PCOS 27 27 0 100
2016 (38)
Papakonstantinou et al., Greece RCT, crossover 12 None 6 vs. 3 53 Impaired glucose 49.3 32.4 26 53
2018 (39) tolerance or T2D
Perrigue et al., 2017 (40) USA RCT, crossover 3 2 wk 8 vs. 3 15 Healthy and obesity 27.1 23.7 0 67
Schlundt et al., 1992 (41) USA RCT, parallel 12 — 3 vs. 2 52 Obesity 18–55 (range) 30.6 0 100
Stote et al., 2007 (42) USA RCT, crossover 8 11 wk 3 vs. 1 21 Healthy 45 23.4 0 67
Verboeket-van de Venne Netherlands RCT, parallel 4 — 4 vs. 2 14 Overweight and 46.1 30.2 NR 100
and Westerterp, 1993 obesity
(43)
Young et al., 1971 (44) USA RCT, crossover 5 None 6 vs. 3 vs. 1 11 Overweight and 22.2 33.5 NR 0
obesity
1
NR, not reported; PCOS, polycystic ovary syndrome; RCT, randomized controlled trial; T2D, type 2 diabetes.
TABLE 2 Specific study characteristics of the included randomized controlled trials1
Schwingshackl et al.
divided into early morning 8.3%, dinner 50%, and a single small contact between
breakfast 8.3%, midmorning 8.3%, snack of 150 kcal to be consumed researchers and
lunch 8.3%, midafternoon 8.3%, when desired participants + dietary
late afternoon 8.3%, dinner 16.6%, records)
midevening 16.6%, and late
evening 16.6%. Guidelines about
how to allocate food into the meal
or snack category were given and
the nine meals were spaced
between 1 and 2 h apart
depending on the subject’s
schedule.
Bachman and Raynor, 7–9 meals/d: 3 meals/d: No No 7–9 meals/d: 1314; Assessed but not
2012 (29) Hypocaloric (1200–1500 kcal/d, Hypocaloric (1200–1500 kcal/d, 3 meals/d: 1217 reported (3-d food
<30 % from fat/d), consume at <30% of kcal from fat/d) records)
least 100 kcal every 2–3 h
Berteus Forslund et al., 6 meals/d: 3 meals/d: No No 6 meals/d: 2150; Assessed but not
2008 (30) Hypocaloric (from the estimated total Hypocaloric (from the estimated total 3 meals/d: 2098 reported
energy expenditure 30% was energy expenditure 30% was (questionnaires,
subtracted to get the prescribed subtracted to get the prescribed telephone interviews)
energy intake). The minimum energy intake. The minimum
energy level prescribed was energy level prescribed was
1400 kcal/d. The prescribed energy 1400 kcal/d). Recommended
level was divided into 3 meals and energy intake in the group of 3
3 snacks, daily energy intake was meals was divided in breakfast,
divided in breakfast 20%, lunch 30% of daily energy intake, lunch
25%, dinner 25% and 3 snacks, 35%, and dinner 35% and no
each snack 10% of daily energy; snacks with the exception of
breakfast 20% + lunch 25% + limited fruit intake and calorie-free
dinner 25% + 3×10% = 100%. drinks.
Cameron et al., 2010 (31) 6 meals/d: 3 meals/d: No No NR Data not collected
Hypocaloric: −700 kcal/d Hypocaloric: −700 kcal/d
Finkelstein and Fryer, 6 meals/d: 3 meals/d: Yes Partly NR Data not collected
1971 (32) Hypocaloric (period 1: 1700 kcal/d; Hypocaloric (period 1: 1700 kcal/d;
period 2: 1400 kcal/d). All meals period 2: 1400 kcal/d). All meals
containing similar amounts of containing similar amounts of
protein, carbohydrate, and fat. protein, carbohydrate, and fat.
(Continued)
TABLE 2 (Continued)
(Continued)
Schwingshackl et al.
Papakonstantinou et al., 6 meals/d: 3 meals/d: No No 6 meals/d: 2081; Adherence to
2018 (39) Eucaloric, weight-maintenance diet; Eucaloric, weight-maintenance diet; 3 meals/d: 1917 Mediterranean diet
daily distribution: 40% daily distribution: 40% score: 32.1 from 55
carbohydrates, 25% protein, and carbohydrates, 25% protein, and
35% fat 35% fat
Perrigue et al., 2017 (40) 8 meals/d: 3 meals/d: No No NR 8 meals: 100%;
Eucaloric (providing all energy as Eucaloric (providing all energy as 3 meals: 96%
evenly spaced eating occasions evenly spaced eating occasions
per day) per day)
Schlundt et al., 1992 (41) 3 meals/d: 2 meals/d: No No NR Whole study group: 71%
Breakfast; hypocaloric 1200 kcal/d. No breakfast; hypocaloric 1200 kcal/d.
Daily distribution: 55% of energy from Daily distribution: 55% of energy from
carbohydrates, 15–20% from carbohydrates, 15–20% from
protein, and 25–30% from fats. protein, and 25–30% from fats.
Stote et al., 2007 (42) 3 meals/d: 1 meal/d: Yes Partly (only dinner 3 meals/d: 2429; Assessed but not
Eucaloric (weight maintenance). Daily Eucaloric (weight maintenance; in study center) 1 meals/d: 2364 reported (daily
macronutrient distribution: 50% minimum fast of 20 h/d). Daily questionnaires)
carbohydrates, 15% protein, 35% macronutrient distribution: 50%
fats. carbohydrates, 15% protein, 35%
fats.
Verboeket-van de Venne 4 meals/d: 2 meals/d: No No 4 meals/d: 1018; Data not collected
and Westerterp, 1993 Hypocaloric, 1000 kcal/d; 300 kcal/d Hypocaloric, 1000 kcal/d, no 2 meals/d: 1090
(43) breakfast, 300 kcal/d lunch (with breakfast, 400 kcal lunch,
option of 100 kcal/d snack), 400 600 kcal dinner.
kcal/d dinner (with option 100
kcal/d snack)
Young et al., 1971 (44) 6 meals/d: 3 meals/d: Yes No NR Data not collected
Hypocaloric, 1800 kcal/d. Daily Hypocaloric, 1800 kcal/d. Daily
macronutrient distribution: macronutrient distribution:
115 g protein, 104 g carbohydrates, 115 g protein, 104 g carbohydrates,
103 g fat. 103 g fat.
1 meal/d:
Hypocaloric, 1800 kcal/d. Daily
macronutrient distribution:
115 g protein, 104 g carbohydrates,
103 g fat.
1
NR, not reported.
FIGURE 2 Network diagrams for body weight (A), waist circumference (B), fat mass (C), and energy intake (D). The size of the nodes is
proportional to the total number of participants allocated to the intervention and the thickness of the lines proportional to the number of
studies evaluating each direct comparison. Moreover, the total number of participants for each comparison is displayed (e.g., the
body-weight comparison of 3 meals/d and 6 meals/d included 7 studies with a total of 251 participants). The number of multiarm studies
for the interventions are indicated by the shade of gray of the background (white for none). s, studies.
Energy intake
No significant differences were observed comparing the Inconsistency
different meal frequencies on energy intake (mainly very low The net heat plots are shown in Supplemental Figures 5–
certainty of evidence) (Figure 3D, Supplemental Figure 4). 7. No relevant inconsistency between designs was observed
Table 3 and Supplemental Tables 1–3 show the certainty for body weight and fat mass. Due to the low number of
of evidence assessment for the direct evidence, indirect comparisons available for the outcome waist circumference,
evidence, and network estimates for all outcomes. it was not possible to investigate inconsistency.