Underfeeding and body weight reg elation in normal-weight young men MELVIN B. HEYMAN, RITA TSAY, LYNDON

VERNON JOSEPH,

R. YOUNG, PA JL FUSS, AND SUSAN B. ROBERTS

Laboratory of Human Nutrition, Massachusetts Institute of Technology, Cambridge, MA 02139; United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston 02111; and Shriners Burns Institute, Boston, Massachusetts 02139 Heyman, Melvin B., Vernon R. Young, Paul Fuss, Rita Tsay, Lyndon Joseph, and Susan B. Roberts. Underfeedingand body weight regulation in normal-weight young men.Am. J. Physiol. 263 (Regulatory Integrative Camp. Physiol. 32): R250-R257, 1992.-The mechanismsof energy regulation invoked by moderate dietary restriction were investigated in sevenhealthy young men of normal body weight leadingunrestricted lives. Following a baseline period of weight maintenance, subjectswere underfed by 806 t 162 (mean t SE) kcal/ day for 21 days. Changesin total energy expenditure (TEE) and resting energy expenditure (REE) and subsequentvoluntary nutrient intakes were measured.The REE, averagedfor fasting and fed states,decreasedduring underfeedingby 100t 29 kcal/ day (P < 0.01). TEE decreasednonsignificantly by 296 rtz170 kcal/day, equivalent to an average of 37% of the decreasein energy intake. Body energy storeswereestimatedto decreaseby 510 t 172 kcal/day (P < 0.03), thus compensatingfor 63% of the dietary energy deficit on average.Voluntary energy intake following dietary restriction increasedabove the initial amount required for body weight maintenance, wasproportional to the weight lossduring underfeeding (P c 0.03)) and wasassociated with a rapid regain of weight lost during underfeeding. These results indicate that energy balance is regulated by adaptive variations in both energy intake and energy expenditure in normal-weight young men leading unrestricted lives but do not support the hypothesis that energy-wasting mechanismscontribute substantially to body energy regulation. doubly labeled water; fat; obesity; energy metabolism; body composition OBESITY is one of the most prevalent

medical disorders in the United States, but its etiology remains unclear. Understanding of the causes of obesity requires information on the normal mechanisms of body weight regulation, in particular the capacity to adapt energy intake or energy expenditure to maintain energy balance in both normal-weight and obese individuals. The extent to which energy expenditure can adapt to an increase in energy intake in normal individuals has been studied extensively, with conflicting results. Some studies indicate that excess dietary energy can be dissipated by diet-induced thermogenesis (1, 16, 27), while other studies do not substantiate a significant role for this mechanism (9, 19). We recently observed that this controversy over the metabolic responses to overfeeding can be related to the experimental procedures used in the different studies and that direct measurements of 24-h energy expenditure uniformly indicate a limited capacity of energy expenditure to adapt to an increase in energy intake (24). One explanation for the finding that energy expenditure does not increase sufficiently to match an increase in energy intake is that adaptive variations in energy expenditure may not contribute significantly to the regulation of energy balance. However, R250

0363-6119/92

there is an alternative explanation which has received little attention: the mechanisms responsible for adaptive increases in energy expenditure with increased energy intake may already be fully operational in healthy individuals of normal body weight living in affluent countries because of wide availability of energy-dense foods that may encourage overeating. If this is true, the capacity for adjusting energy expenditure should be quantifiable by measurement of the decrease in energy expenditure in response to reduced energy intake. Furthermore, and of relevance to this issue, we have recently observed (22) that young adult men of normal body weight typically consume and expend substantially more dietary energy than the current recommended dietary allowances (17) indicate is necessary for their body size and reported level of physical activity. This study was designed to test the hypothesis that energy-wasting mechanisms contribute significantly to body weight regulation in normal-weight young men leading unrestricted lives and that these mechanisms can be observed as a decrease in energy expenditure when energy intake is reduced. This investigation differs from previous studies (2, 5, 6, 11, 12, 15, 29) by examining normal-weight young men leading unrestricted lives, a group that may be most likely to exhibit adaptive variations in energy expenditure. We employed a moderate energy deficit (800 kcal/day) within the range of day-to-day and between-subject variations in energy intake (7) and utilized recent methodological advances (25) to measure the changes in all of the principal components of energy balance. METHODS Subjects. Seven male students (2 white, 2 Hispanic, 2 Asian Indian, and 1 black) of normal body weight (Table 1) completed the 13-wk study. None smoked,had any recent illnessor history of an endocrinopathy, or were taking any medications.At the time of the study all were healthy asjudgedby a normal history, physical examination, and routine blood and urine examinations. Subjects were interviewed by a nurse, dietitian, and physician to determine motivation to follow the study protocol. The study was conducted in the Clinical Research Center (CRC) at the MassachusettsInstitute of Technology with approval from the MIT Committee on the Use of Human as Experimental Subjects. Written informed consent was obtained from the subjects. Protocol. The subjectswere able and encouragedto pursuea normal lifestyle during the study, and all continued their usual occupations. They were required to sleep at the CRC for the nights before measurementsof resting energy expenditure (REE, describedbelow) but otherwise remained at their usual residence.Physical activity wasmonitored but wasnot restricted.

$2.00 Copyright 0 1992 the American Physiological

Society

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UNDERFEEDING

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Table 1. Subject characteristics Parameter

Values

7

ke, yr

20.8;+0.5 69.2-1-4.2 174.9k5.5 22.6t0.7

Starting weight, kg Height, cm Body mass- index, kg/m2 ..-. .-.----Values are means & SE; n, no. of subjects.

The study was divided into three phases (Fig. 1). During phase I, which lasted for 10 days, each subject’senergy intake for body weight maintenancewasdetermined.Phase 2 lastedfor 21 days and started within 1 mo of the end of phase 1. Each

subject was requestedto maintain body weight between these phases.During phase 2, each subject consumed~800 kcal/day (3,350kJ/day) lessthan during phase I. Phase 3 lastedfor 7 wk, and was consecutive with phase 2. Voluntary food intake was measuredduring the first 10 days ofphase 3, and after this time long-term trends in body weight and anthropometric variables weremonitored. Total energy expenditure (TEE) wasmeasured throughout phases 1 and 2 using the doubly labeledwater technique (25). Complete 24-h urine collections were made during this time. All urine wascollected in dark containersto which 14 ml 11.4 N HCl had been added, with the exception of daily specimensrequired for the doubly labeledwater analyses,which were collected in nonacidified dark bottles. Forty-eight-hour fecal sampleswere collectedduring the last 3 days ofphase 1 and once each during the first and secondhalves of phase 2 and stored at -20°C prior to analysis. Physical activity was monitored qualitatively in phases 1 and 2 and during the first 10 days of phase 3 using motion recordersworn around the waist (Caltrac, Hemokinetics, Madison, WI) and the wrist of the nondominant hand (Timex model 101 motion recorder, Kaulins and Willis, Middlebury, CT). During these periods, subjectskept a record of the duration and types of strenuousphysical activities performed. Body weight (-t-l00 g) was measureddaily during phase 1 and on at least 5 days each week in phase 2. These measurementswere taken while the subjects were wearing a standard hospital robe, before they had breakfast and after they had voided. In addition, body weight and standard anthropometric measures(waist, hip, mid-upper arm, thigh, and calf circumferencesand triceps, biceps, subscapular,and suprailiac skinfold thicknesses)were recorded in the morning before the subjectshad consumedbreakfast and after they had voided on study days 0, 10, 20, 29, 41, and then at approximately weekly intervals until the end of the study. Diets. All food and caloric beveragesconsumedby the subjects during phases 1 and 2 and the first 10 days of phase 3 were provided by the CRC. Meals contained normal food items and a palatable low-protein liquid supplement(phase 1 only) divided 1 PHASE Study day

0 1

Energy intake (provided)

weight &ntena&e4

111

PHASE

10 I

20 I

2

1

PHASE3

30 I

weight maintenance r-r, nus 6uu Kcal/aay

40 I //

77 I

ad *+Mum

*

Activity monitors Total energy expenditure

+

Resting metabolic rate/ thermic effect of meal Urine collection

** 4

*

* b

Stool collection Anthropometry

*

Fig. 1. The study design.

*****

REGULATION

R251

between3 mealsplus an eveningsnackeachday. Three different daily menus were provided to the subjects. The menus were tailored to individual preferencesfor foods. The liquid supplement, consisting of orange sherbet, safflower oil, hydrous dextrose, and unsweetenedKool-aid (GeneralFoods,White Plains, NY), provided 806 kcal/day of grossenergy; ~1% of the energy was from protein, 45% of the nonprotein energy was from fat, and 55% of the nonprotein energy was from carbohydrate. Coffee, tea, and table salt were included in the menusin fixed daily amounts if they formed part of the subjects’normal diets. At least one meal per day was consumedin the CRC, and other mealswere consumedin the CRC or at the subjects’residences. No alcohol waspermitted during the first 40 days of study. The nutrient contents of the diets provided during phase 1 were designedto mimic a typical high-protein, high-fat American diet (3). Approximately 1.5 g/kg body weight of mixed protein wasprovided, and an averageof 55% of the nonprotein energywasderived from carbohydrate and 45% from fat. During the first 7 days of phase 1, the energy intake required for weight maintenance was determined. The initial energy intake provided was basedon a dietitian’s estimate of requirements(14). Subjects were allowed to leave partial portions of food if they felt unusually satiated (theseportions were saved for composition analysis; seebelow) or request extra portions if they felt unusually hungry. Measurementsof body weight were taken, and appropriate adjustments to energy intake were made to maintain weight within 500 g of the value on day 0 if trends in body weight were observed.During the last 3 days of phase 1, subjectswere given the calculated averageof energy consumed during the first 7 days, with the dietary composition specified above, and were required to completely consumeall portions of food and rinse and scrapeall food containers. During phase 2, subjectswere provided with the menusfixed on the last 3 days of phase 1, with the exception that the lowprotein liquid supplementwasremoved from the menuto give a prescribedgrossenergy deficit of 806kcal/day. Compliancewith the dietary regimen was of concern during this phase,because subjectswere often hungry and had many opportunities to consumedisallowedfoods,sincethey werefree-living. We addressed this issuein two ways. First, the subjectshad considerablecontact with the investigators, who gave frequent reinforcement about the importance of compliance.Second,the urine osmolar excretion rates in complete 24-h urine collections in thesesubjects were measuredand comparedwith expected values that were predicted from the known dietary intakes of protein and sodiumand potassiumsalts (thesenutrients constitute the majority of the osmolarload). In a validation study (21), the relationship between dietary constituents and urine osmolarexcretion rate did not vary significantly between subjects in the present investigation and subjects from two other studies in which compliance was assured,either by continuous residence in a metabolic ward and observation at mealtimesor by the use of the p-aminobenzoic acid compliancetest (23) during overfeeding. During the first 10 daysofphase 3, subjectswere requestedto consumeas much or aslittle food and drink asthey required to feel normally satiated, and they were given specific instructions to not deliberately changetheir diet to gain the body weight lost during phase 2. Subjects were specifically instructed not to weigh themselvesduring the first 10 days of phase 3. As in phases 1 and 2, a 3-day menuplan wasprovided, but the number of items of food included in the menu was increasedthreefold, and subjectswereallowedto specify asmany or asfew itemsand number of portions as they wished to eat. They were not required to completely consumethe portions, and food not consumedwas savedfor composition analysis.After these 10 days, subjectsprovided their own food and could regulate their body weight as they desired.

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R252

UNDERFEEDING

AND

ENERGY

Freeze-dried, homogenized portions of identical replicas of menus given to the subjects in phases 1 and 2, the left-over foods,and fecal sampleswere analyzed for grossenergy by adiabatic bomb calorimetry. The measuredgrossenergy contents of the 3-day menucycleswere 1.6 t 0.6% (P < 0.02) lower than values calculated using information on the fat, protein, and carbohydrate contents from food tables (USDA Handbook No. 465, Release3, 1983), assumingenergy contents of 9.46, 4.65, and 3.97 kcal/g for fat, protein, and carbohydrate, respectively. Apparent digestibleenergy intakes during phases 1 and 2 were calculated as the measuredgross energy minus fecal energy. Metabolizable energy (ME) intakes were then calculated asapparent digestible energy intake minus urinary nitrogen x 7.9. The group averageenergy digestibility was 95.48% of grossintake in phase 1 and 95.47%in phase 2. Thesevalues were used to calculate each subject’sdigestible energy intake, since individual collections would not be reliable becauseof the short collection time. ME intakes during phase 3 were calculatedfrom the weights of foods provided and grossenergy contents estimated from food composition data (USDA Handbook No. 465 Release3, 1983; corrected for the difference between grossenergy calculated from food tables and measuredby bomb calorimetry in individual subjectsfor the phase 1 menus)and from the grossenergy contents of the leftover foods. In this calculation it wasassumed,as in phase 1, that the apparent digestibility of energy was95.48%and that body nitrogen balancewasat equilibrium. Measurements of REE. 0, consumption (VO,) and CO, production (VCO,) were measuredunder thermoneutral temperature conditions in the fasting and fed states on four occasions during the study, twice during the last 3 days of phase 1 and once each during the first and secondhalves of phase 2. The measurementswere made using an open-circuit indirect calorimeter (Deltatrac, SensorMedics,Anaheim, CA) that was calibrated at regular intervals using mixed reference gasesof known concentration. Subjects were instructed to relax and avoid hyperventilation, fidgeting, and sleepingduring measurements.The measurementsduring the fasted state were madefor 20 min before breakfast, 11.5 t 1.7 h after the last meal on the previous day. After the fasting measurements,subjects consumedtheir usualstudy breakfast containing exactly 25% of the daily intakes of protein, fat, and carbohydrate. Thirty minutes after the start of breakfast, the measurementsof VO, and VCO~ wereresumedand continued during 20 min of every 30 min until 4 h after the start of breakfast. Subjectsremainedresting during the lo-min breaks. During one of the calorimetry sessionsin each phase,small serial blood sampleswere drawn through an indwelling catheter inserted into an antecubital vein at least 15 min before the start of calorimetry measurements. Values for REE were calculated from each determination of VO, and VCO~ using Weir’s equation (30). Two estimatesof the 24-h REE were made for each study period. Estimate 1 was calculated from the mean of all 20-min determinations for the study day. Estimate 2 was an unweighted 24-h estimate determined by assumingthat the 24-h day consisted of four 4-h energy-expenditure cycles as measuredbetween breakfast and the end of the measurement,plus an 8-h period during which energy expenditure decreasedlinearly from the final determination of energy expenditure in the sessionto the initial fasting value (24). Measurements of TEE. Three sequential IO-day doubly labeledwater studies(25) were conductedin eachsubjectto measure TEE throughout phases 1 and 2, as describedin detail by Roberts et al. (24). Mixed 2H2180dosescontaining 0.15 g/kg of H2180and 0.06 (measurement 1) or 0.055 (measurements 2 and 3) g/kg 2H20 were given orally midmorning on study days 0, 10, and 20 and were followed with two 50-ml rinses of local tap water. Subjectsconsumedbreakfast before the dosesweregiven

REGULATION

and were fasted for at least 3 h after the administration of isotope. Urine specimenswere collected before administration of each isotopedose,at 3, 4, and 5 h after each isotopeadministration, and thereafter at approximate daily intervals between isotopedosesuntil study day 30. Abundancesof 2H and IsO in dilutions of the isotopedosesand in at least 19 urine specimens per subject (baseline,5-h and l-, 2-, 8-, 9-, and IO-day samples for each isotope study) were analyzed using isotope-ratio mass spectrometry (SIRA-10, VG Isogas, Middlewich, Cheshire, UK). The samplescollected at 3 and 4 h after dosingwere not analyzed routinely becausepreliminary analysesindicated that the isotopeswere not fully equilibrated in urine at these times. Sampleswerepreparedfor 2H/1H analysisusingthe zinc reduction technique and for 1802/1602analysis in CO, using the H,O-CO, equilibrator system (31). On average, quadruplicate analysesof each sample were performed. The coefficients of variation for day-to-day repeatedmeasuresof 2H and 180abundanceswere 0.2 and 0.8%0,respectively. The doubly labeledwater data wereprocessedasdescribedby Robertset al. (24), usingDLW software (4), asrecommendedby the International Dietary Energy Consultative Group (18). Rate constants and intercepts for isotope disappearancewere calculated usinga nonlinear least squaresmodel,and isotopedilution spaceswere calculated from the intercept data using the equation of Halliday and Miller (13). Carbon dioxide production rates (rC0,) werethen calculatedusingEq. A6 of Schoelleret al. (26). The value for total body water (N) used in the equation wasdetermined asdescribedby Schoelleret al. (26) (i.e., H2180 space/l.Ol), with a small correction for changesin body water during the measurementperiod madeby assumingproportional changesin body weight and water (20). Values for TEE were calculatedfrom rC02 with Weir’s equation (30), usingestimates for a food quotient corrected for body fat mobilization or deposition during the measurement(mFQ). The estimate for fat mobilization is calculatedby solving equationsfor TEE, respiratory quotient (RQ), and ME intake simultaneously. Body composition. Energy balancesduring both phases 1 and 2 were determinedasthe difference betweenthe measuredrates of ME intake and TEE. This method provides determinations for energy balance that are comparableto those obtained by measuringchangesin body density (24). Nitrogen balancewas determined during underfeeding in phase 2 as described(24). For this measurement,the nitrogen contents of pooled 24-h urine collectionsobtained during phases 1 and 2 and of the food aliquots were determined using a modification of the Kjeldahl technique involving microwave digestion of the samples(Kjelfast, CEM, Matthews, NC). Forty-eight-hour stool collections were analyzed for nitrogen content, and averagedigestible nitrogen was determined for the group of subjectsas the meanof the individual values for percent digestibility in each study phase.Digestible nitrogen intakes were calculated from gross intakes using the measuredaveragedigestibility of 90.79% in phase 1 and 91.73% in phase 2 (comparablewith a published value of 92%; seeRef. 7). Nitrogen balancewas assumedto be zero during phase 1, and miscellaneousnitrogen losses(in sweat, hair, nails) were calculated for each subject as the difference between nitrogen intake (corrected for apparent digestibility) and nitrogen output in urine. Thesefactors werethen appliedto phase 2 data, to calculate nitrogen balance as the difference betweenthe digestibility-corrected nitrogen intake and the sum of nitrogen losses(urine plus miscellaneous).Protein balance wascalculated as nitrogen balance X 6.25. Statistical analyses. Values are expressedas means * SE. Differences between measurementsand phaseswere analyzed using one-way analysis of variance (ANOVA), ANOVA for repeated measures,and Student’s paired t test. Regressionanalysis was usedto assessassociationsbetween measurementsin the three phasesof the study. Differences betweengroupswere

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UNDERFEEDING

AND

considered significant at P < 0.05. The calculations formed using CLINFO software (BBN Software Cambridge, MA).

were perProducts,

ENERGY

R253

REGULATION 2

G s5.1

RESULTS

Table 2 shows the values for measured ME intakes and nutrient intakes calculated from food weights and published food composition data during weight maintenance in phase 1, during underfeeding in phase 2, and during the first 10 days of phase 3 when food intake was ad libitum. ME intakes were significantly lower in phase 2 than in phase 1 and were nonsignificantly higher in phase 3 than in phase 1 (P = 0.09). Values for ME intake were significantly greater in phase 3 than phase 1 for the 6 subjects who lost ~0.1 kg during phase 2 (4,036 t 209 vs. 3,394 t 257 kcal/day, respectively; P < 0.03.) The higher ME intake in phase 3 was due to higher intakes of carbohydrate and protein. The changes in body weights of the subjects are shown in Fig. 2. Body weights increased during phase 1, although during the period when dietary energy requirements were being established (days 1 to 7), body weights did not change significantly and individual values were within 500 g of initial values as specified in the study protocol. Body weight decreased significantly during phase 2, averaging 96.6 t 23.8 g/day (P < 0.01). There was no significant difference between the rates of weight loss in the first and second lo-day measurement periods of phase 2 (P = 0.79). Substantial variation was observed between subjects in mean weight lost throughout the underfeeding period, ranging from 4.8 to 185.7 g/day. Within the first 10 days of phase 3, all subjects had reestablished their baseline weight, and by day 41 of the study, the mean weight was essentially the same as at the beginning of underfeeding (70.3 t 4.1 compared with 69.7 & 4.0 kg, respectively; P = 0.21). Throughout the remainder of phase 3, weight variation equaled the variation observed during phase 1. The mean weight at the end of the - II-wk study (70.5 t 4.2 kg) was also similar to that observed at the start of phase 2. None of the subjects reported consciously trying to regain weight lost during underfeeding. Weight gain was significantly more rapid than weight loss: +257.1 t 36.2 g/day (phase 3) compared with -96.6 t 23.8 g/day (phase 1) (P < 0.005). Table 3 shows the within-subject variance in the measurements of TEE, fasting REE, and 24-h REE, calculated as described in METHODS from the mean of data from the fasted and fed states. There was little variance in the repeated measurements in each phase for the deterTable 2. Energy and nutrient intakes during weight maintenance (phase 1), underfeeding (phase 2), and 10 days following underfeeding (phase 3) Phase

Gross energy, kcal/day Metabolizable energy, kcal/day Protein, g/day Fat, g/day Carbohydrate, g/day

3,808&292 3,647+259 104&6 155tl2 430t33

Values are means & SE. Significantly 1: * P < 0.001, 7 P < 0.01.

1

Phase

2

Phase

3

3,140+293* 2,860&260*

4,333+192t 4,044+177

103&6 123&11* 33lt31*

134+8-t 133k6 584+30t

different

from

values

for phase

Study

Day

Fig. 2. Body weight change from study day 0. Values are means & SE. ** P < 0.01 compared to values at the start of underfeeding on study day 10.

Table 3. Within-subject variance in energy measurements in phases 1 and 2 Phase

Resting energy expenditure Fasting 24-h REE* Total energy expenditure Values are means & SE in kcal/day, * See text for calculations.

1

Phase

-17t20 -33t20 REE,

resting

2

-4&21 6t33 -262tl87 energy

expenditure.

minations of fasting and 24-h REE but considerable variance in values for TEE in phase 2. Table 4 summarizes data on energy expenditure and physical activity throughout phase 1 and during each half of phase 2 (days lo-19 and 20-29), using the means of repeated energy expenditure measurements in each phase. No difference was found between the first and second halves of phase 2 for any of the parameters. The fasting REE in kilocalories per day was significantly lower during phase 2 than in phase 1, and values remained significantly different when expressed per kg of fat-free mass. The estimated 24-h REE, calculated as described in METHODS from the mean (estimate 1) or unweighted mean (estimate 2) of data from the fasted and fed states, was significantly lower in phase 2 than in phase 1 (100 kcal/day on average). RQ by calculation procedure 1 was significantly lower in phase 2 than in phase 1. The values for RQ are comparable to the RQs estimated from dietary intake and body fat balance (4). TEE did not differ significantly between phases but was lower by 296 kcal/day, on average, and tended to be lowest during the second half of phase 2. Considerable individual variability was observed in TEE differences between phases 1 and 2. Thus the 95% confidence limits for the difference were relatively large: -712, + 120 kcal/day. Individual values for TEE, REE and body weight change in phase 2 are shown in Table 5. Table 6 summarizes the energy balance and estimate of body composition changes of the subjects during underfeeding in phase 2. The mean decrease in ME intake below that required for weight maintenance in phase 1 was 786 kcal/day. This value was very similar to the energy deficit calculated as the difference between ME intake in phase 2 and TEE in phase 1 (806 kcal/day), indicating that on average the subjects were in energy

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Table 4. Summary of the energy expenditure data (study

Phase 1 days O-9)

(study

Phase 2 days 10-19)

(study

Phase days

2 20-29)

Calorimetry data Fasting REE, kcal/day 1,724+83t 1,658+87 1,654+81 Fasting REE, kcal/kg fat-free mass per day 28.8&0.7* 27.7t0.8 27.6k0.8 0.848t0.009* 0.804kO.008 RQ, 24-h 0.814t0.005 24-h REE 1, kcal/day$ 2,0871tlO3* 1,985&106 1,991+112 24-h REE 2, kcal/day$ 2,047+100* 1,950+104 1,946kllO Doubly labeled water data 2,447fl48 Mean H,lXO space, mol 2,447&162 2,457&156 Rate of 2H disappearance, day-l 0.08856kO.00432 0.08678zkO.0022 1 0.08146~0.00540 Rate of 180 disappearance, day-l 0.11669kO.00434~ 0.11296t0.00268 0.10607t0.00651 Modified food quotient 0.85lzkO.005" 0.824t0.009 0.834+0.008 TEE, kcal/day 3,667+316 3,501+344 3,239+332 TEE, kcal kg fat-free mass-l day-l 60.7t3.3 57.7t4.1 53.8k5.2 2.llt0.13 2.09t0.14 TEE/REE 1.95kO.18 13.2tl.5 11.9kl.7 12.4tl.5 Body fat, % Activity data Caltrac trunk monitor, kcal/day 2,927+179 2,846+224 2,600+239 Wrist motion sensor, units/day 3,875&l ,654 3,895kl,206 4,268k 1,690 Reported strenuous activity, min/day 40.828.5 43.8t4.5 36.2k4.8 Values are means t SE. RQ, respiratory quotient; TEE, total energy expenditure. Significantly different from values for mean phase 2 values (days lo-29 combined): * P < 0.05; t P < 0.01; there was no significant difference between values ofphme 2 (days 10-19) and phase 2 (days 20-29). $ See text for calculations. l

l

Table 5. Individual values for energy expenditure and weight change during underfeeding Phase

Phase

1

2 (Mean)

Subject TEE

3,855 2,507 4,510 4,361 3,599 2,554 4,280

REE

(fasting)

REE

1,679 1,465 1,734 1,985 1,595 1,557 2,051

Mean 1,724 3,667 t SE 2316 t83 Values for phase 1 and phase 2 are in kcal/day.

(24 h)

Energy (kcal/day) ME intake Calculated energy deficit 24-h REE 1* 24-h REE 2* TEE Body energy loss Body composition (g/day) Weight Fat (by difference from energy and nitrogen balances) Protein (by nitrogen balance)

(fasting)

REE

(24 h)

Weight (phase

Change, 2 -phase

2,802 2,013 4,116 3,866 3,825 2,698 4,272

1,623 1,439 1,639 1,933 1,558 1,422 1,975

1,930 1,719 2,004 2,377 1,873 1,652 2,358

-0.1

2,087 HO3

3,370 k325

1,656 t83

1,988 &lo8

-2.0 kO.5

body composition during underfeeding Means

REE

1,943 1,739 2,187 2,423 2,055 1,837 2,426

Table 6. Summary of changes in energy balance and Parameter

TEE

+ SE Values

-786t7 806tl62 -99t30 -lOOk -296&170 -5lOtl72 -96.6k23.8 -48.4k19.2 -9.2t2.7

Energy content of weight loss, kcal/g 4.77k2.53 ME, metabolizable energy. Calculated energy deficit = ME intake during phase 2 - TEE in phase 1. * See text for calculations.

balance during phase 1. Underfeeding resulted in a mean decrease in REE of ~5%, equivalent to 12% of the energy deficit. No significant decline was observed in energy expended for physical activity (estimated as the difference between TEE and REE), consistent with the lack of significant changes in activity measured by the motion

kg 1)

-1.9 -2.2 -1.2 -1.4 -3.5 -3.9

sensors (Table 4). The mean body energy loss resulting from underfeeding, calculated from the difference between ME intake and TEE during underfeeding, accounted for an average of 62% of the deficit in energy intake. Fat and protein stores were estimated to constitute 50% and IO%, respectively, of body weight loss during underfeeding. During the first half of underfeeding, total body water, indicated by the H2180 dilution space change, decreased an average 17.5 g/day. This value is approximately half of the difference between the average weight loss (96.6 g/day) and fat plus protein depot losses (57.6 g/day) during phase 2, not an unexpected discrepancy, since all the methods used were independent. The energy content of the weight loss was estimated to be 4.31 -+ 2.75 and 5.22 t 4.40 kcal/g weight loss for the first and second lo-day periods of phase 2, respectively (mean = 4.77 t 2.53 kcal/g). Individual values for the dietary energy deficit during underfeeding (calculated as the difference between ME intake during phase 2 and TEE in phase 1) did not relate significantly to values for body energy loss during underfeeding, although a tendency for a relationship between the dietary energy deficit and body energy loss during underfeeding was observed using a polynomial equation

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UNDERFEEDING

AND ENERGY

(r2 = 0.61). No significant relationship was observed between weight loss or the subsequent increase in energy intakes and initial body fat content or physical activity determined by the activity monitors or the activity records. A significant linear relationship was observed between weight loss during phase 2 and the difference between ME intake in phase 3 and TEE in phase 1 (Fig. 3). DISCUSSION

The regulation of energy balance must involve adaptive fluctuations in energy expenditure or energy intake over periods of several days or longer, since diet digestibility is relatively unaffected by energy intake, and day-to-day variations in energy intake and expenditure differ substantially (7). However, the issue of whether the primary factor maintaining energy balance is energy intake or energy expenditure remains a subject of major controversy. In a recent study, we observed only a limited capacity of normal-weight young men to adapt to an increase in energy intake by increasing energy expenditure (24). Therefore, the primary purpose of the present investigation was to determine the capacity for energy expenditure adaptation to decreased energy intake. We anticipated that the capability for adaptation of energy expenditure might be more apparent during underfeeding than during overfeeding. Most previous studies that have addressed the question of whether energy expenditure can substantially adapt to a decrease in energy intake have used energy deficits so extreme that compensation would clearly be impossible, have studied underfeeding following a period of overfeeding, or have focused on obese or overweight individuals who may have defective thermogenesis (2,5,6,12,15,29). Relatively little information has been published on the capacity of energy expenditure to adapt to a moderate decrease in energy intake within the range of typical energy intake observed between normal, healthy individuals (11). Furthermore, that study was conducted under restrictive conditions in a metabolic ward, which may have suppressed any mechanisms of energy regulation associated with physical activity and thermoregulation. An important feature of our study was that subjects were permitted to lead normal lives throughout the investigation, so that any potential for energy regulation by 2000 c3 1500

ii

1

z .-c D

1000 1

/jj

0

2

1

Weight

Loss

in Phase

,

,

3

4

2 (kg)

Fig. 3. Relationship between weight loss in phase 2 and the excess energy intake in phase 3 (calculated as the difference between metabolizable energy intake in phase 3 and total energy expenditure in phase 1) (r2 = 0.666;

P < 0.03).

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adaptive variations in energy expenditure for physical activity and thermoregulation (8, 28) would not be suppressed. The use of the doubly labeled water method to measure changes in TEE was also a critical component of the study, because other techniques for the estimation of TEE are less direct and may fail to detect quite substantial changes in energy expenditure. The issue of whether the subjects were compliant with the prescribed dietary regimens while they were free-living was addressed through frequent contact between the investigators and the subjects and by the use of our new test of dietary compliance involving measurement of urine osmolality (21) In the group of subjects taken as a whole, we observed evidence of a modest decrease in energy expenditure in response to decreased energy intake. Energy expenditure for physical activity and thermoregulation (calculated as the difference between TEE and REE) decreased by 296 kcal/day, but this amount was not significant due to the high between-subject variability. REE averaged for fasting and fed states decreased significantly but compensated for only 12%, on average, of the energy deficit. The combined changes in energy expenditure for resting metabolism and physical activity compensated for an average of 37% of the decreased energy intake. Body energy stores, determined as the difference between ME intake and TEE, were thus mobilized to compensate for the majority (63% on average) of the dietary energy deficit. Thus, despite the fact that the subjects were able to lead essentially normal lives, only about a third of the energy deficit was compensated for by a reduction in energy expenditure, and the remainder was mobilized from body energy stores. Consequently, any energy-wasting mechanism operating in these subjects would have to be viewed as somewhat ineffective in regulating energy balance over the 2Lday underfeeding period, since body nutrient mobilization compensated for most of the dietary energy deficit. This finding is consistent with the results from previous studies of extreme dietary energy restriction in normal adults and in obese individuals (2,5, 6, 11, 12,15,29) and from observations of the association between energy intake and body weight in normal individuals (10). This indicates that nonobese young men, like obese individuals, do not possess energy-wasting mechanisms that are normally operational and can be switched off to compensate fully for reduced energy intake during dietary restriction over a period of 21 days. Our study does not address the question of whether a longer-term underfeeding period would demonstrate a greater capacity for energy expenditure conservation. However, long-term underfeeding induces substantial body weight loss and therefore may not provide an appropriate model of normal body weight regulation in which fluctuations in body weight should be relatively small. In contrast to the finding of a modest involvement of adaptive variations in energy expenditure in the regulation of energy balance during underfeeding, we found evidence for a significant role for long-term adaptive variations in voluntary nutrient intakes following underfeeding in these normal subjects. After underfeeding, the

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R256

UNDERFEEDING

AND

voluntary energy intake of our subjects increased above that consumed during weight maintenance and was associated with a rapid repletion of weight lost during undereating. Subjects increased energy intake despite being encouraged to refrain from purposely gaining weight. The high correlation of intake during weight repletion with weight loss during underfeeding (Fig. 3) demonstrates a remarkable ability of the individual subjects to return to their usual body weight. While we cannot rule out the possibility that subjects were consciously increasing their food intake, we believe this unlikely, since all reported eating a normal amount of food relative to phase 1 and, in addition, did not want to regain the body fat lost during undereating. It is noteworthy that these young healthy subjects of diverse ethnic backgrounds uniformly did not select a high-fat diet during the increased energy intake in phase 3. Instead, they chose a diet in which 29% of energy was provided by fat. The loss of body weight noted in phase 3 of our earlier overfeeding study (24) therefore appears unlikely to be due to nutrient-specific satiety, since the subjects in this underfeeding study increased their carbohydrate and protein intake to more than compensate for the decreased fat intake in phase 3. Further studies are needed to address the issue of whether low energy expenditure following underfeeding contributed to the rapid weight gain. In summary, results from this investigation and from our previous overfeeding study (24) indicate that the regulation of energy balance in free-living, normal-weight young adult men occurs through both adaptive variations in energy expenditure and subsequent energy intake, but that variations in energy intake may be the primary means by which energy balance is maintained. Additional investigations are needed to explore the extent to which these findings are applicable to other population groups and to further investigate the effects of moderate fluctuations in body energy balance on body composition. We thank the nursing staff at the Massachusetts Institute of Technology Clinical Research Center (CRC), in particular Pat Carroll, who provided many hours of expert nursing assistance, the CRC and HNRC laboratories, the CRC kitchen staff, and the subjects themselves without whom the study could not have been completed. This project was supported by National Institute on Aging Grant AG-07388. The computer facility at the General Clinical Research Center, University of California, San Francisco (funded by the Division of Research Resources, 5 MO1 RR-00079) was also utilized. Present address of M. B. Heyman: Dept. of Pediatrics, Div. of Gastroenterology & Nutrition, Univ. of California, San Francisco, San Francisco, CA 94143-0136. Address for reprint requests: S. B. Roberts, Massachusetts Institute of Technology, El7-613, 40 Ames St., Cambridge, MA 02111. Received

1 July

1991; accepted

in final

form

16 January

1992.

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Underfeeding and body weight regulation in normal-weight young men.

The mechanisms of energy regulation invoked by moderate dietary restriction were investigated in seven healthy young men of normal body weight leading...
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