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Keywords:

  • meal frequency;
  • adiposity;
  • leptin;
  • fatty acids;
  • respiratory quotient

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

Objective: To investigate in man the consequence on body composition and related biological and metabolic parameters of omitting or adding a meal.

Research Methods and Procedures: Twenty-four young normal-weight male subjects were recruited, 12 usual four-meal and 12 usual three-meal eaters, differing only in the consumption of an afternoon meal. They omitted or added a fourth meal during a 28-day habituation period and were asked to report their intake on three 3-day occasions. Before and after this habituation period, subjects participated in a session with a time-blinded procedure, and blood was collected continuously from lunch to the spontaneously requested dinner. Body composition, respiratory quotient, and biochemical parameters were measured in the late evening preceding each session.

Results: Omitting a meal was followed by increases in fat mass (360 ± 115 grams, p < 0.05), late evening leptin concentration (20.7 ± 11.0%, p < 0.05), and respiratory quotient (3.7 ± 1.4%, p < 0.05). Increase in the percentage of dietary fat during the habituation period (+4.1 ± 2.0%, p < 0.05) was correlated with fat mass (r = 0.66, p < 0.05). Adding a meal had no effect, but, in both groups, the change in energy content at this fourth eating occasion was correlated with the change in adiposity.

Discussion: Our results suggest that adiposity may increase when young lean male subjects switch from a four- to a three-meal pattern by removing their usual afternoon meal. This effect could be partly mediated by a change in the macronutrient composition of the diet.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

The influence of eating frequency on body composition has provided relatively consistent results in animals. For example, in rats, more fat-free mass and less fat mass are gained for a similar body weight when food intake is fractionated in several small meals instead of few big meals (1, 2, 3). If these data are relevant to human eating, this would mean a lower body fat for a similar body weight and may have important consequences in terms of public health because it is established that body fat rather than body weight per se is the primary cause of increased morbidity (4). Such a beneficial result could, therefore, be reached by a simple change in the daily number of meals. Some success for this strategy has been reported in children (5). However, attempts to increase meal frequency and match energy intake for weight loss in obese subjects have led to discrepant results (6, 7, 8, 9, 10, 11, 12), but some authors have reported that increasing eating frequency improves energy compensation (13) and appetite control (14, 15). Although only correlatives, it is of note that data from cross-sectional surveys commonly show a negative relation between adiposity and eating frequency (16, 17, 18, 19, 20). Metabolically, ingesting the same energy in more frequent meals has been reported to reduce mean insulin concentrations and improve glucose tolerance (for review, see (21)), flatten lipogenesis-lipolysis peaks and nadirs (22, 23, 24), and lead to more favorable plasma lipid profiles (25, 26).

In most of these studies, energy intake was fixed, a procedure that does not enable assessment of eating behavior (27). This condition may not be relevant to the actual metabolic effects of a change in eating frequency in a real world situation. Another important point is that the eating episode has to be a meal and not a snack or, in other terms, an eating episode driven by a physiological need and not triggered by the presence of food or other psychological factors. Several studies suggest that consumption of snacks may contribute to obesity (28, 29, 30, 31, 32, 33), but this is not a consistent finding (34). We have found that eating in a no-hunger state, as is often the case when snack foods are consumed, is not compensated for at the next meal (35, 36, 37). Moreover, we have reproduced in the laboratory a common situation where humans spontaneously eat available food without any prior hunger sensation (38) and we have found that, contrary to the meal, this intake is not preceded by the normal preprandial decrease in glucose concentrations (39). The confusion between meal and snack intakes could, therefore, explain why epidemiological studies sometimes fail to note any benefit of a high meal frequency or a detrimental effect of snack consumption.

The present study was designed to determine whether a change in the usual meal frequency of young and healthy male subjects would result in changes of adiposity and associated biological parameters. To be as relevant as possible to real life conditions, we modified meal frequency of subjects only by asking them to omit from or to include in their usual eating pattern an afternoon eating occasion known in France as the goûter. This eating occasion generally distinguishes four- and three-meal eaters in this country, leading to a doubling of the lunch and dinner intermeal interval in the latter group. It is consumed by most children (40) but persists in only ∼30% of adults (41). We have shown that, in the usual goûter eaters, this eating occasion has the characteristics of a meal; i.e., hunger triggered and preceded by a fall in glucose (38). Moreover, epidemiological studies have noted that the daily consumption of a goûter is associated with a lower BMI (41, 42). Thus, this eating occasion can be considered as an interesting tool to study the influence of a change in eating frequency in humans.

Because the circadian peak in leptin concentration occurs in the middle of the night (43) and there are no reports on the relation between leptin during this time period and the biological and anthropometric parameters usually associated with leptin, we included a late evening measurement of all variables. This circadian leptin cycle being food-driven, a dinner meal had to be provided to subjects beforehand.

Research Methods and Procedures

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

Subjects

After approval of the procedure by the Ethics Committee in Human Research at the Hôpital du Bocage in Dijon, subjects were recruited through advertisements posted at the Faculties of Science and Medicine. To be included, subjects had to be male, healthy, and ranging in age between 19 and 25 years and in BMI between 19 and 24 kg/m2. Smokers, trained athletes, subjects who drank alcohol more than occasionally, who had food allergies, and who took medication were excluded from the study. Subjects were also excluded if they reported a personal or family history of obesity, eating disorders, diabetes or other metabolic diseases, or a change in body weight > 3 kg over the 3 years before the study. All subjects had to have scores <6 on the dietary restraint, disinhibition, and hunger subscales of the Three-Factor Eating Questionnaire (44). Other factors of exclusion were the fear of blood withdrawal and aversion for any of the provided foods. The quality of the selection was a necessary condition for the study to be conclusive. To be considered as a meal, the first criterion was that this eating occasion had to be impossible or very difficult to skip. This criterion was required for the goûter, i.e., the fourth meal. Thus, subjects had to take this meal every day of the week.

Practically, all candidates were screened using an autoquestionnaire in which all their eating habits were explored. To avoid any dissimulation, they were not told which eating patterns were required. They were told that on the session day, they would receive the number of meals that they usually consumed, so that it was important for them to give us their actual eating pattern. Before completing this questionnaire, they were not told that we would request to add or omit one of their meals during the following month. In this questionnaire, questions were asked for each meal.

Only subjects who answered that they always ate something between 4 pm and 5:30 pm, have always done so, sometimes eat at home, and eat because they are hungry were selected for the goûter group. Only subjects who answered that they never eat something between lunch and dinner and do not eat because they are not hungry were selected for the non-goûter group.

When a candidate fit the selection criteria for one of the groups, he was provided with a diary in which he had to note the amount and the time of all intakes during 5 days. Diaries were then checked by the investigator.

From these candidates, 24 were selected after the diary report, 12 with a four-meal per day pattern and 12 with a three-meal per day pattern. The only meal differing between these groups was the goûter. This excluded any intake of food between lunch and dinner in the three-meal pattern. They all gave written informed consent before the experiment and were financially compensated for completing the study.

Study Design

Subjects participated in two experimental sessions [Session 1 (S1)1 and Session 2 (S2)], separated by a 28-day habituation period. In S1, subjects were studied on their usual meal frequency (four for the four-meal pattern group and three for the three-meal pattern group). Subjects were then asked to change their meal frequency during the next 28 days (habituation period) so that the four-meal pattern group omitted the goûter, whereas the three-meal pattern group added a goûter to their meal pattern. The first group will be referred to as the four- to three-meal frequency (4to3MF) group and the second as the three- to four-meal frequency (3to4MF) group. To avoid introducing a snack (intake not induced by hunger) in the 3to4MF subjects, we reduced the size of each individual lunch in this group by 30%. Each lunch during the habituation period was taken in the laboratory and included a main dish, yogurt, and bread designed so that the energy content was 70% of the usual energy intake at this meal as stated on the 5-day diary report. Thus, in S2, the 4to3MF subjects were tested on a three-meal pattern and the 3to4MF subjects on a four-meal pattern.

Blood Sampling and Plasma Assays

On the experimental day, blood was withdrawn continuously using a specially designed double-lumen catheter (MTB, Amstetten, Germany) inserted into the antecubital vein as previously described (45). Heparinized blood was continuously withdrawn throughout the session at a flow rate of 1.5 mL/5 minutes through a peristaltic pump. The heparin flow was 7 IU/mL blood. The tubes were changed every 5 minutes. Blood samples were then immediately centrifuged at 2500g for 15 minutes at 4 °C, and plasma was pipetted into four different tubes and frozen to −30 °C for subsequent assays. The late evening blood sample was drawn by a single puncture and treated as described above.

All assays employed commercially available kits. Glucose, triacylglycerols (TAGs), and non-esterified fatty acids (NEFAs) were measured using a selective multiparametric analyzer (Lisa 200; Hycel, Pouilly-en-Auxois, France). Glucose was determined by the glucose-oxidase enzymatic method (Hycel kit). TAGs and NEFAs were quantified using a colorimetric enzymatic method (kit C, Wako, both 5% accuracy; Oxoïd, Dardilly, France). Insulin concentration was determined by radioimmunoassay using the SB-INSI-5 kit (7% accuracy, sensitivity of 2 μIU/mL; CIS Bio International, Gif-sur-Yvette, France). Leptin was determined by a double-antibody radioimmunoassay method (Sensitive Human Leptin kit; Linco Research, Inc., St. Charles, MO), with intra- and inter-assay coefficients of variation of 3.5% and 5.3%, respectively.

Foods

On the evening preceding the session day, a mixed complete meal was to be chosen by subjects: rice with chicken, fish and peas (paella; Findus Co., Noisiel, France), or semolina with sausages, chicken, and vegetables (couscous; Findus Co.). Yogurt (Danone Co., Le Plessis-Robinson, France) and bread were available for completing the meal. For the session day's breakfast, each subject was served food items he usually consumed according to his diary report. Most frequently, it was bread with butter and jam, milk and cereals, fruits, and biscuits. At lunch, the test meal consisted of pasta with meat and tomato sauce (Spaghetti Bolognaise; Findus Co.) and praline-flavored dessert cream (Mont Blanc). In the 4to3MF group, the goûter consisted of food items usually consumed by subjects as noted in their diaries. It was often biscuits, fruits, bread, and chocolate. In the 3to4MF group, most subjects consumed the biscuits provided at the laboratory for their newly created goûter over the 4-week period. Thus, in S2, the goûter was composed mostly of biscuits (LU, Danone Co.). Dinner consisted of beef pieces with potatoes (Findus Co.), with bread, stewed apple (Andros Co., Biars, France), and biscuits (Palets Bretons, LU, Danone Co.). All items were served in large portions. Water was provided ad libitum. All items were weighed to the nearest 0.1 grams on a Mettler scale (Mettler-Toledo, Inc., Columbus, OH) before serving, and overall consumption was determined by subtracting the weights of any leftovers.

Anthropometry

Body composition was determined by whole-body DXA using a Hologic QDR 4500 apparatus (Hologic Inc., Waltham, MA). Scans were analyzed with Hologic software version 8.07. No food or liquid was allowed after the end of dinner, and subjects had to void their bladders before the examination. Based on previous reports (e.g., (46, 47)), the delay between the end of the meal and the DXA measurement (i.e., mean 210 minutes, always at the same hour within subjects) was considered as sufficient for most of the meal to be emptied from the stomach and was in a similar range as that in the Pritchard et al. study (48) on the evaluation of DXA. A Step Phantom calibration (Capintec Inc., Ramsey, NJ) was performed daily as recommended by the manufacturer. Measurements were made with the subject supine on the scanning table, wearing only underpants and no metal objects. Measurement time was 7 minutes. The same investigator performed all scans.

Gas Exchanges

Late evening respiratory quotient (RQ) was measured by means of an open circuit ventilated hood system with subjects lying in the supine position. Gas analyses were performed by a paramagnetic oxygen analyzer for O2 and an infrared carbon dioxide analyzer for CO2 (Elonex, London, United Kingdom). Measurements were recorded online using dedicated software (Breeze version 3.2). The delay between the end of the meal and the RQ measurement was, on average, 350 minutes. This was considered satisfactory because previous work (49, 50) with similar energy loads as in the present study have shown that the RQ reaches its preprandial level between 240 and 300 minutes after a meal. Fifteen minutes before the start of the measurement, subjects were requested to lie down and become accustomed to the facial mask (Hans Rudolph Inc., Kansas City, MO). Measurements were performed for 15 minutes, and the last 10 minutes were used to calculate RQ.

Motivation to Eat

Hunger was assessed using 100-mm visual analog scales preceded by the question “Do you feel hungry?” and anchored with “not at all” and “extremely” at the left and right ends, respectively. The distance from the extreme left to the subject's vertical dash represented the rating score, expressed in millimeters. Scales were rated every 30 minutes, but some scales were intercalated at random to avoid time cues.

Food Intake Reports

Three weeks before the experiment, subjects completed a 5-day diary in which they were asked to carefully note all their intakes, specifying time of consumption, commercial name of the items, and amount eaten. This was checked with each subject on submission of the diary. This was then used to check whether the subjects never ate between lunch and dinner or ate a goûter on a regular basis. During the habituation period between S1 and S2, this diary was completed again in three 3-weekday periods (P1, P2, and P3), one period every 8 days. Weekend days were excluded due to the usual alterations in eating habits observed during these days.

Procedures

Four subjects (two from each group) were tested in each session. They came to the laboratory on the evening before the session day at 7 pm and received an evening meal at 8 pm. Foods provided at this meal were the same in S1 and S2, but amounts eaten were freely chosen and assessed by weighing plates before and after consumption. For all meals taken at the laboratory, subjects were encouraged to eat as much or as little as they wanted. Body composition was assessed between 11 pm and 12 am. Each subject was then installed in a separate individual 3- × 4-m room. Gas exchanges were measured between 12 am and 1 am, followed immediately by the blood sampling. In both S1 and S2, these data were collected at the same time for each subject. The subjects were then allowed to sleep. They were woken at 8 am, and at 8:15 am they had their usual breakfast, i.e., foods that they usually consumed at home. During the morning, they were allowed to meet until 11:30 am. They were then seated in comfortable armchairs and isolated in their individual rooms, which were quiet and comfortable enough for reading and study. They were then deprived of time cues as previously described (35, 36, 37, 38, 51, 52). Between 12:30 pm and 1 pm, but at the same time for each subject, a catheter was inserted in an antecubital vein of the forearm, and blood withdrawal was started and continued uninterrupted throughout the experiment. Lunch was served 30 minutes after the first blood sample. Subjects were required to ask for their next meal whenever they wanted. According to session and to group, one or two meals were expected, but subjects were asked to base their request only on their feeling of hunger. Foods typically consumed at the goûter and at dinner were served for the first and second requested meals for four-meal eaters and foods typically consumed at the dinner for three-meal eaters. Moreover, to avoid any premature request, subjects were told that they would not be allowed to leave the laboratory before 10 pm. Approximately 30 minutes after the end of dinner, the catheter was withdrawn.

Statistical Analyses

Statistical analyses were conducted using SYSTAT software (version 7.01; SPSS, Chicago, IL). All results were expressed as means and SE. Anthropometric data, late evening blood concentrations, and RQ were analyzed using univariate ANOVA, with sessions (S1 and S2) as within-subject factor and group (3to4MF and 4to3MF) as between-subject factor. To verify whether the effect was actually valid for each group, planned analyses within each group were conducted using Student's t tests for paired samples when a session effect or a group interaction was significant.

The biological parameters were subjected to a step-wise analysis according to the recommendation of Matthews (53). In the present study, we constructed three variables for the concentrations of glucose, insulin, TAG, NEFA, and leptin during the intermeal interval: an area under the curve (AUC) using the trapezoidal method, a mean concentration by dividing the sum of the concentrations by the number of tubes, and a pre-goûter profile that comprised the concentrations during the 30 minutes before the goûter request, the same time interval being studied in the no-goûter session to allow comparisons between sessions. This provided information on: 1) the total amount of substrates and hormones between lunch and dinner; 2) the mean concentration during this interval; and 3) the potential preprandial decline or dynamics as described previously (38, 54). Because the total rather than the incremental amount is of physiological importance in our studies (55), the basal AUC was not subtracted from the calculated AUC. The AUCs and means of these concentrations were then analyzed using Student's t tests for paired samples, as were all intake parameters. The blood profiles before the goûter and over the same interval in the no-goûter session were analyzed by a linear polynomial regression. Pearson correlations between results were calculated on the within-subject data. The entry criterion was fixed at p < 0.05.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

Some variables in some subjects could not be included in analyses. First, one subject in the 4to3MF group was excluded for lack of compliance, and his data were not analyzed. His diary showed that he had often forgotten to omit his goûter. He did not give any explanation but the difficulty to abstain from eating in the afternoon. For information, his usual goûter was neither very high nor very low energy. For three subjects (one from the 4to3MF group and two from the 3to4MF group), problems occurred with the blood collection on one of their sessions. Thus, intermeal blood data analyses were conducted on 20 subjects. Lastly, food diaries from two subjects were not correctly completed; therefore, diary reports were analyzed on 22 subjects.

Anthropometry

Before the experimental period, no significant difference in body weight or in body composition was found between groups. For fat mass, the ANOVA showed an effect of the session factor without interaction with the group factor [F (1, 21) = 4.21, p < 0.05]. Compared with S1, fat mass of the 4to3MF subjects had increased in S2 by 360 ± 115 grams (p < 0.05) (Table 1). This corresponded to an increased percentage in fat mass of 0.44 ± 0.20% (p < 0.05). No change was observed in the 3to4MF group. In S2, the difference between groups failed to reach significance.

Table 1. . Anthropometrical data on sessions 1 and 2 (mean ± SE)
4to3MF (n = 11)3to4MF (n = 12)
 Session 1Session 2Session 1Session 2
  • SE, standard error; 4to3MF, four- to three-meal frequency; 3to4MF, three- to four-meal frequency.

  • *

    Significantly different from session 1, p< 0.05.

Body weight (kg)68.32 ± 1.4168.82 ± 1.4669.82 ± 1.6069.94 ± 1.52
BMI (kg/m2)21.66 ± 0.3721.86 ± 0.3921.67 ± 0.4421.71 ± 0.43
Fat mass (kg)10.11 ± 0.9310.47 ± 0.95*9.23 ± 0, 759.33 ± 0.78
Fat mass (%)15.05 ± 1.2915.49 ± 1.40*13.35 ± 0.9613.48 ± 1.00

Eating Behavior

On Session Days

On session days (Figure 1), breakfast was not altered by the change in meal frequency in either group. In the 4to3MF group, lunch was 690 ± 184 kJ (p < 0.005) and dinner 953 ± 150 kJ (p = 0.0001) higher in S2 than in S1. In the 3to4MF group, the difference between lunches illustrated the mandatory 30% reduction in energy content of this meal, whereas the reduction at dinner (−673 ± 347 kJ) only approached significance (p = 0.06). Overall, total energy intake of the 4to3MF group decreased between sessions (−991 ± 456 kJ, p < 0.05), whereas in the 3to4MF group, there was a slight but non-significant increase (+1191 ± 673 kJ; p = 0.08).

image

Figure 1. Mean energy intake (±SE) at breakfast, lunch, goûter (when present), dinner, and cumulated over 24 hours in the 4to3MF (A) and 3to4MF (B) groups for each session. In the 3to4MF group, energy content of the lunch was adjusted to 70% of normal for this meal to trigger a goûter request. All other meals were ad libitum. In S1, the 4to3MF subjects were in their usual four-meal pattern and the 3to4MF subjects in their usual three-meal pattern. In S2, the 4to3MF group had omitted the goûter, and the 3to4MF group added a goûter during 28 days. Goûter and dinner were freely requested. * p < 0.05 between sessions.

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In the 4to3MF group, the interval between lunch and dinner (Figure 2) was 68 ± 20 minutes shorter in S2 than in S1 (p < 0.01), whereas it was 36 ± 18 minutes (p < 0.05) longer in the 3to4MF group.

image

Figure 2. Duration of the interval between the end of lunch and the dinner request in each session. The goûter request is also represented when present. * p < 0.05 between sessions.

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Outside the Laboratory

Before the experiment, energy intake determined from the 5-day diaries (Table 2) was higher in the four-meal eaters than in the three-meal eaters (p < 0.005). Carbohydrates accounted for most of this difference (p < 0.005) and protein for a smaller part (p < 0.05). Compared with the pre-experimental period, the 3to4MF group increased (p = 0.005) and the 4to3MF group decreased (p < 0.05) their daily energy intake in P1, but this difference failed to reach significance in P2 and P3.

Table 2. . Energy and macronutrient intakes before and during the habituation period (mean ± SE)
Habituation period
 BaselineP1P2P3
  • SE, standard error; P1, Period 1; P2, Period 2; P3, Period 3; 4to3MF, four- to three-meal frequency; 3to4MF, three- to four-meal frequency.

  • *

    Significantly different from baseline, p< 0.05.

  • Significantly different from 4to3MF group, p< 0.05.

4to3 MF    
 Energy intake (MJ)11.3 ± 0.49.6 ± 0.5*9.5 ± 0.49.9 ± 0.6
 Carbohydrate (%)48.9 ± 2.242.1 ± 2.2*46.5 ± 1.746.1 ± 2.1
 Fat (%)36.1 ± 2.140.5 ± 1.9*36.8 ± 1.737.3 ± 1.7
 Protein (%)14.9 ± 0.617.2 ± 0.8*16.7 ± 0.5*16.6 ± 0.5
3to4MF    
 Energy intake (MJ)9.7 ± 0.210.5 ± 0.4*10.5 ± 0.410.4 ± 0.4
 Carbohydrate (%)45.3 ± 1.151.0 ± 1.4 *,51.3 ± 1.2 *,49.5 ± 2.0*
 Fat (%)39.2 ± 1.134.8 ± 1.5 *,34.4 ± 1.3*35.9 ± 1.8*
 Protein (%)15.6 ± 0.314.2 ± 0.5 *,14.3 ± 0.5 *,14.6 ± 0.5

At the macronutrient level, omitting the goûter in the 4to3MF group was associated in P1 with a decrease in the percentage of carbohydrate (p = 0.001) and an increase in the percentage of protein and fat (both p < 0.05). This difference was still significant for protein in P2 (p < 0.05) but not in P3. For the 3to4MF group, adding a meal led to a similar result in P1, P2, and P3, i.e., an increase in the percentage of carbohydrate (all p < 0.001) and a decrease in the percentage of protein (p < 0.005, p < 0.01, and p < 0.05, respectively) and fat (p < 0.005, p < 0.005, and p < 0.05, respectively). This resulted in a significantly higher percentage of protein and fat in the 4to3MF group than in the 3to4MF group in P1. This difference was significant for carbohydrate and protein in P2 and for protein in P3 (all p < 0.05).

Late Evening RQ

There was no difference in RQ between groups before the experiment (Figure 3). The ANOVA revealed an interaction between sessions and groups [F (1, 21) = 5.11, p < 0.05]. Comparisons showed that in the 4to3MF group, the RQ was significantly increased by 0.028 ± 0.008 (3.7 ± 1.4%, p < 0.05) in S2 compared with S1, whereas no change in RQ was observed in the 3to4MF group. In S2, the difference between groups failed to reach significance.

image

Figure 3. Late evening RQ in each session. * p < 0.05 between sessions.

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Blood Variables

Late Evening Concentrations

The ANOVA revealed a session effect or an interaction with the group factor only for plasma leptin [F (1, 21) = 5.46, p < 0.05]. Comparisons showed that mean leptin concentration was significantly increased in S2 compared with S1 only in 4to3MF subjects (Table 3). In S2, the difference between groups failed to reach significance.

Table 3. . Late evening concentrations of blood variables (mean ± SE)
4to3MF (n = 11)3to4MF (n = 12)
 Session 1Session 2Session 1Session 2
  • SE, standard error; 4to3MF, four- to three-meal frequency; 3to4MF, three- to four-meal frequency; TAG, triacylglycerol; NEFA, non-esterified fatty acid.

  • *

    Significantly different from session 1, p< 0.05.

Glucose (mM)5.43 ± 0.245.50 ± 0.115.65 ± 0.145.87 ± 0.15
TAG (mM)1.16 ± 0.160.99 ± 0.080.84 ± 0.081.11 ± 0.11
NEFA (mM)0.14 ± 0.030.10 ± 0.020.14 ± 0.010.19 ± 0.04
Insulin (μU/mL)26.50 ± 2.9026.10 ± 3.4023.10 ± 2.6021.30 ± 3.60
Leptin (ng/mL)3.37 ± 0.594.06 ± 0.73*3.20 ± 0.683.35 ± 0.63
Intermeal Concentrations

In both groups, mean plasma glucose and insulin (Figure 4) were higher when subjects were on a four- than on a three-meal frequency (p < 0.005), this difference being significant only in the 4to3MF group for insulin (p = 0.001). In contrast, mean NEFA concentration was lower on a four- than on a three-meal frequency (p < 0.05), this difference being significant only in the 4to3MF group for TAG (p < 0.05) and failing to reach significance in the 3to4MF group (p = 0.08).

image

Figure 4. Mean plasma glucose, insulin, TAG, NEFA, and leptin concentrations calculated from the continuous blood withdrawal during the interval between lunch and dinner. * p < 0.05 between sessions.

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Similar results were found for plasma glucose and insulin AUCs (data not shown), i.e., a higher level when subjects were on a four- than on a three-meal frequency (p < 0.01 and p = 0.01 for 4to3MF and 3to4MF groups, respectively), this difference being significant for insulin only in the 4to3MF group (p < 0.05). No differences were found for TAG, NEFA, and leptin.

Preprandial Concentrations at the Goûter

In both groups, there was a significant linear decrease in glucose concentration before the goûter request, i.e., in S1 in the 4to3MF group and in S2 in the 3to4MF group [F (1, 11) = 13.46, p < 0.005 and F (1, 9) = 11.02, p < 0.01, respectively]. This was associated with a significant linear decrease in insulin concentration [F (1, 11) = 8.75, p = 0.013 for the 4to3MF group and F (1, 9) = 6.39, p < 0.05 for the 3to4MF group]. No changes were observed in the other variables. It should be noted that there were no changes in glucose and insulin concentrations during the same time window within subjects in the other session, i.e., when subjects had no goûter.

Relations between Variables

Body Composition and Other Variables

First, we verified that there was no correlation between the changes in fat mass and energy intake at dinner meal. Across sessions and groups, fat mass was correlated with late evening leptin and NEFA concentrations (r = 0.92, p < 10−7 and r = 0.36, p = 0.01, respectively). Moreover, BMI and fat-free mass were also correlated with late evening leptin concentrations (r = 0.58, p = 10−5 and r = −0.35, p = 0.01, respectively). The correlations were also significant between fat mass and mean leptin concentration (r = 0.83, p < 10−4) and AUC (r = 0.80, p < 10−4) during the intermeal interval.

In the 4to3MF group, fat mass was correlated with the change in fat (r = 0.663 and r = 0.636 in S1 and S2, respectively, both p < 0.05) and carbohydrate intakes (r = −0.677 and r = −0.668 in S1 and S2, respectively, both p < 0.05) during P1. Interestingly, this change in percentage of carbohydrate intake during P1 was correlated with late evening leptin concentrations (r = −0.659 and r = −0.682 in S1 and S2, respectively, both p < 0.05), but during P2 and P3, the changes in macronutrient intake were no longer correlated with body composition or leptin levels. Moreover, in this group, the change in fat mass between sessions was correlated with the change in late evening leptin concentration (Figure 5A), the energy intake from the omitted goûter (Figure 5B), and the change in RQ (r = −0.77, p < 0.01). The change in fat-free mass was correlated with the energy from the goûter (r = −0.81, p = 0.005; data not shown).

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Figure 5. Correlations between the changes in fat mass (in percentage) and in late evening plasma leptin concentrations between sessions for the 4to3MF group (A) and 3to4MF group (C) and in energy content of the goûter omitted (in the 4to3MF group; B) or added (in the 3to4MF group, D).

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In the 3to4MF group, there was a negative relation between the changes in fat mass and in late evening leptin concentration (Figure 5C) or the energy intake from the added goûter (Figures 5D), whereas the relation with these two variables was positive with fat-free mass (r = 0.86, p < 0.005, data not shown). The change in fat-free mass was correlated with the change in AUC of glucose concentration (r = 0.69, p < 0.05; data not shown).

RQ and Other Variables

In the 4to3MF group, but not in the 3to4MF group, the change in RQ was correlated with the changes in BMI (r = 0.72, p < 0.01), fat-free mass (r = 0.80, p = 0.001), fat mass (r = −0.62, p < 0.05), late evening glucose (r = 0.77, p = 0.005), and NEFA (r = −0. 64, p < 0.05) concentrations. No correlation was found in the 3to4MF group.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

This study was designed to determine whether a change in meal frequency as modest as one meal per day during 28 days would lead to changes in body composition and associated biological and behavioral parameters. This hypothesis was derived from previous studies indicating that the longer the intermeal interval, the greater the contribution of NEFA to metabolism (56). In this view, the increase in fat mass would be a metabolic adaptation for increasing fat oxidation in response to increased fat intake (49). It was hypothesized that the same mechanism may also enhance fat oxidation on omission of a meal.

That the goûter was a true meal in the four-meal eaters (4to3MF group) was supported by the linear decline in glucose concentration in S1. This profile (or more accurately named, this dynamic) has been repeatedly shown to be present before a meal (39, 54) and is not observed before consumption of a snack presented in the usual satiety period (38). To circumvent the possibility of the added goûter being taken as a snack (an eating occasion occurring in a normal satiety period) and not a meal (35), we reduced lunch intake by one-third in the three-meal eaters (3to4MF group). This procedure was effective because in S2, the spontaneous request of the goûter was also preceded by preprandial declines in glucose concentrations. Interestingly, as in our previous study (38), the decline in glucose concentration was always associated with a decline in insulin concentration.

Most changes were observed in the four-meal eater group who switched to three meals per day by omitting the goûter. In this group (4to3MF), mean fat mass, late evening leptin concentration, and RQ increased between sessions by 3.3 ± 1.3%, 20.7 ± 11.0%, and 3.7 ± 1.4%, respectively. Energy intake at lunch and dinner was also higher in S2 than in S1 but not enough to compensate for the energy of the omitted goûter. Percentages of protein and fat in the diet were also increased during the first one-third of the habituation period. The causal role of omission of a meal in the change in body composition was supported by the positive correlation between the level of daily energy to which the goûter contributed before the experiment and the change in fat mass; the higher the energy intake at the goûter, the higher the gain in fat mass on omission of the goûter. Looking at individual data, fat deposition occurred mostly when omitting this meal represented a high energy challenge. It is important to note that such a relation was not found for other meals, arguing for the specific role of the omitted meal. Thus, not only the duration of the intermeal interval but also the level of exogenous energy usually provided during this intermeal interval will contribute to fat deposition. One other hypothesis would be that the individuals most likely to gain fat mass might be those with largest energy intake at this fourth meal. However, this hypothesis would be contradictory with the fact that before the experimental period, there was a negative correlation between the energy intake at this fourth meal and fat mass (r = −0.62, p = 0.033). Thus, subjects with high energy intake at the fourth meal seemed to be less likely to have body fatness, but skipping this meal produced a high fat depot. In contrast, switching from three to four meals per day was not associated with any significant mean alterations in fat deposition.

Authors have previously reported an increase in fat mass without any increase in energy intake (1, 2), but, in our study, it is striking that these changes in body composition were associated with a lower daily energy intake. Although we asked our subjects not to change their life habits, a reduction in physical activity may have occurred. Epidemiological studies have found that goûter eaters are more active than non-goûter eaters (41, 42), but the relation may be circumstantial. Further work is required to determine whether a modification in spontaneous activity is associated with a reduction in meal frequency. A decrease in thermogenesis is also unlikely because no difference has been found in previous studies between subjects with a high vs. a low eating frequency (57). Last, this discrepancy could be only artifactual. Intake reports are subjected to criticism for their uncertain accuracy, especially for total energy intake. For example, it is likely that under-reporting of energy intake increases when the number of meals decreases (58). For the sessions taking place in the laboratory, the necessity to compensate on so few food items (two at lunch, two at dinner) may have impaired the phenomenon because conditioning on sensory properties of food is a major factor of amount eaten and needs several assays to occur. Eating so much of a single food may have overreached the satiation boundary for this food and impaired compensation (which was significant but partial). Accurate compensation is observed only when a large variety of food items is available. We had chosen to limit the number of food items to two because our previous studies showed that the relationship between leptin (52) or pharmacological agents (59) and food intake is observed mainly for the first food of the meal.

The mechanisms by which adiposity may increase when eating frequency is reduced have been the subject of various hypotheses, mainly involving an insulin-dependent mechanism. Mean insulin concentrations are reduced and glucose tolerance is improved when the same energy is ingested in more frequent meals (60, 61). In view of the role of insulin in fat deposition, less insulin would mean a lower adiposity. However, this was observed in a highly fractioned diet pattern and fixed intake conditions, whereas with a one- vs. five-meal pattern (15), no difference was reported. In a free food intake situation, as in the present study, subjects who omitted one meal spontaneously consumed more energy on a four-meal pattern, rather than on a three-meal pattern, and insulin was consistently elevated. This was not specific to the omitting procedure because a similar difference was noted in the other group. Moreover, insulin was not correlated with any of the anthropometric data.

Our study provides another hypothesis for this increase in fat mass. Subjects who switched from four to three meals per day spontaneously increased the proportion of fat in their diet. Fasting periods are known to modify macronutrient selection in favor of dietary fat in animals (62). A similar change in macronutrient selection has been reported with higher fat and lower carbohydrate percentages in the spontaneous diet when subjects were switched from a high to a low-frequency eating pattern (24, 63). During Ramadan, which is characterized by a >12-hour intermeal interval during a month, an increase in the percentage of energy derived from fat has also been observed (64). The role of dietary fat in obesity is controversial (for opposite arguments, see (65, 66)), but there is a body of evidence that fat is at least an aggravating factor for other risk factors of weight gain. Our results show that this change in fat and carbohydrate percentages of the diet during the habituation period was correlated with the change in fat mass, with positive and negative coefficients, respectively. This argues for a contribution of this increase in the fat proportion of spontaneous energy intake in the increased adiposity. This is further supported by the observation that the greater the increase in glucose AUC between sessions, the greater the gain in fat-free mass. In France, two studies have noted that goûter eaters have higher carbohydrate intake (41, 42), and the consequence on body composition of removing the goûter from their eating pattern, as is usually observed during adolescence, may depend on the maintenance of this carbohydrate intake in the diet. The role of alteration in the choice of food items rather than eating frequency per se had been previously raised by Murphy et al. (67). Our results are in line with this hypothesis. The notion that changing meal frequency affects food choice does not deny its role on energy homeostasis, although it does indicate a possible mechanism. A change in macronutrient intake was also observed in the 3to4MF group, i.e., increased percentages of carbohydrate and decreased percentages of fat and protein. Analyses of the intake data showed that most of these changes could be attributed to the mandatory reduction in the energy content of lunch, a meal usually high in protein and fat, whereas food items at the goûter were high in carbohydrate. This procedure was chosen because there were no experimental data showing that adding an eating occasion in a usual intermeal interval would lead to the creation of a meal in a homeostatic way, i.e., reduction of energy intake at the other meals to equilibrate energy balance at the same level as beforehand. Thus, to be sure that this eating occasion would be a meal, it had to be triggered by a physiological hunger signal as described in a previous work (38), the most secure way being to reduce the usual energy load of a subject's lunch meal. This limits the relevance of this improved macronutrient composition in 3to4MF subjects, but it is interesting to note that this group had a similar percentage of fat in their diet on the last of the experimental weeks (35.9 ± 1.8%) as the 4to3MF subjects before the experiment (36.1 ± 2.1%). This suggests that this is the stable macronutrient composition reached on a four-meal frequency.

Subjects who omitted their midafternoon meal increased energy intake at lunch and at dinner. In rats (68), Le Magnen found that when a usual meal was omitted daily, they progressively increased their intake at the previous meal, displaying an anticipatory behavior from conditioning to the sensory properties of foods. Our results demonstrate for the first time, to our knowledge, that an anticipatory appetite is also operant in humans in free-living conditions, although this compensation was only partial. It is of note that these results were obtained using session day data rather than diary reports, which are less sensitive than laboratory conditions for detecting such changes.

Our findings also provide new insight on the relations between leptin and body composition. First, fat mass was more strongly correlated with late evening plasma leptin than with any diurnal leptin time-point. Second, in the 3to4MF group, the individual changes in fat mass and late evening leptin concentrations were negatively correlated, but there was a strong positive correlation between leptin and fat-free mass. This relation is particularly unusual. Although fat-free mass has been shown to contribute to leptin variance (69), this contribution is weak. However, fat mass is not the only determinant of leptin concentrations. There is much evidence that high carbohydrate intake and consecutive blood glucose concentrations have a potent action on leptin secretion (70, 71, 72). Consistently, in this group, the difference in AUC glucose was positively correlated with the change in fat-free mass. Thus, nocturnal leptin concentrations should be interpreted not only in terms of adiposity but also of glucose disposal during the previous day.

A last result is the increase in carbohydrate oxidation as estimated by the RQ in the 4to3MF group. We measured the late evening RQ because its circadian nadir usually occurs during the night (73). Moreover, given the negative relation between fat mass and RQ (74), this was considered as the most relevant for the detection of small changes in substrate oxidation. Across subjects, the RQ was in a narrow range (0.771 ± 0.02), evidencing a metabolism in which fat and carbohydrate contributed 77% and 23%, respectively. In the 4to3MF group, glucose and NEFAs were correlated with the RQ with positive and negative coefficients, respectively. Moreover, the changes in fat-free mass and fat mass also correlated with the change in RQ, with positive and negative coefficients, respectively. This suggests that the more that fat mass is gained, the more that fat oxidation will increase during the midnocturnal period. Longer-term studies will be needed to find out whether fat mass would have continued to increase and whether RQ would have returned to its pre-experimental value.

In conclusion, our results show that reducing meal frequency of lean male subjects by only one meal per day during 1 month induced a rapid but transitory increase in spontaneous dietary fat, fat gain, and midnocturnal leptin increase. These changes could be adaptative, allowing metabolism to face longer intermeal intervals through increased fatty acid disposal. Switching from a three- to a four-meal pattern by decreasing intake at lunch did not induce any change. These results suggest that individuals having a usual four-meal pattern could be at risk of gaining adiposity if they shift to a lower meal frequency, a hypothesis that would require assessment in future studies.

Acknowledgement

  1. Top of page
  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

This work was supported by the French Ministry of Research and Technology and by Danone Co. (Danone-Vitapole). We thank Laurent Brondel for assistance during the late evening measurement of gas exchanges, Annie Jaeger for technical help with the equipment, Aline Fuselier for assistance during the session days and the habituation period, and Nicole Colas-Linhart and Anne Petiet, without whom the insulin and leptin measurements would not have been possible. We are grateful to the subjects for their commitment throughout the study.

Footnotes
  1. Nonstandard abbreviations: S1, Session 1; S2, Session 2; 4to3MF, four- to three-meal frequency; 3to4MF, three- to four-meal frequency; TAG, triacylglycerol; NEFA, non-esterified fatty acid; RQ, respiratory quotient; P1, Period 1; P2, Period 2; P3, Period 3; AUC, area under the curve.

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  2. Abstract
  3. Introduction
  4. Research Methods and Procedures
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References
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