Acute response to oral calcium loading in pregnant and lactating women with a low calcium intake: a pilot study.

UNLABELLED: This pilot study in women from The Gambia with low habitual calcium intakes showed differences in calciotropic hormones between pregnant, lactating and non-pregnant, non-lactating women similar to those in Western women. The response to oral calcium loading indicates a high degree of calcium conservation independent of reproductive status. INTRODUCTION: In pregnancy and early lactation, parathyroid hormone (PTH) concentrations may be suppressed. Uncertainty exists about how calcium metabolism is regulated, particularly when calcium intake is low. METHODS: We investigated fasting markers of calcium metabolism and the acute calcemic and calciuric responses after an oral calcium load in 30 pregnant, lactating or non-pregnant, non-lactating (NPNL) Gambian women with low habitual calcium intakes. Women received 1 g elemental calcium (CaCO3) at 0 min. Blood was collected at -30 and 180 min. Urine was collected from -60 to 0, 0-120 and 120-240 min. Samples were analysed (blood: ionized calcium (iCa); plasma (p): total calcium (tCa), phosphate (P), creatinine (Cr), PTH, 1,25-dihydroxyvitamin D (1,25(OH)2D), osteocalcin (OC), ß C-terminal cross-linked telopeptide of type 1 collagen (ßCTX), cyclic adenosine monophosphate (cAMP); urine (u): Ca, P, Cr, cAMP). RESULTS: Pre-loading, groups did not differ significantly in iCa, pP, uCa/Cr and uP/Cr. pOC concentrations were significantly lower and NcAMP and p1,25(OH)2D higher in pregnant women; pPTH and pßCTX in lactating women were higher than in NPNL women. Post-loading, iCa, ptCa and uCa/Cr concentrations increased; pPTH, NcAMP, ßCTX and uP/Cr decreased in all groups, but the magnitude of change did not differ significantly between groups. CONCLUSION: Differences between pregnant, lactating and NPNL Gambian women in pPTH, NcAMP and p1,25(OH)2D and bone markers were similar to Western women. However, the response to calcium loading indicates that there may be no differences in renal and intestinal calcium economy associated with reproductive status, potentially due to a high degree of calcium conservation associated with low intakes.

Energy adaptations in human pregnancy: limits and long-term consequences.

The very slow rate of human fetal growth generates a lower incremental energy stress than in any other mammalian species. This creates a situation in which adaptive changes in metabolic rate and in the amount of additional maternal fat stored during gestation can make a profound difference to the overall energy needs of pregnancy. Comparisons of women in affluent and poor countries have recorded mean population energy needs ranging from as high as 520 MJ to as low as -30 MJ per pregnancy. These energy costs are closely correlated with maternal energy status when analyzed both between and within populations, suggesting that they represent functional adaptations that have been selected for their role in protecting fetal growth. Although this metabolic plasticity represents a powerful mechanism for sustaining pregnancy under very marginal nutritional conditions, it must not be construed as a perfect mechanism that obviates the need for optimal nutritional care of pregnant women. The fact that fetal weight represents up to 60% of total pregnancy weight gain in many pregnancies in poor societies (compared with a well-nourished norm of 25%) indicates that the fetus is developing under suboptimal nutritional and physiologic conditions. It has long been recognized that this has immediate consequences for the offspring in terms of increased perinatal mortality. The more recent appreciation that impaired fetal growth may also precipitate longer-term defects in terms of adult susceptibility to noncommunicable and infectious diseases reinforces the view that pregnancy may be the most sensitive period of the life cycle in which nutritional intervention may reap the greatest benefits.

Metabolic response to experimental overfeeding in lean and overweight healthy volunteers.

Possible adaptive mechanisms that may defend against weight gain during periods of excessive energy intake were investigated by overfeeding six lean and three overweight young men by 50% above baseline requirements with a mixed diet for 42 d [6.2 +/- 1.9 MJ/d (mean +/- SD), or a total of 265 +/- 45 MJ]. Mean weight gain was 7.6 +/- 1.6 kg (58 +/- 18% fat). The energy cost of tissue deposition (28.7 +/- 4.4 MJ/kg) matched the theoretical cost (26.0 MJ/kg). Basal metabolic rate (BMR) increased by 0.9 +/- 0.4 MJ/d and daily energy expenditure assessed by whole-body calorimetry (CAL EE) increased by 1.8 +/- 0.5 MJ/d. Total free-living energy expenditure (TEE) measured by doubly labeled water increased by 1.4 +/- 2.0 MJ/d. Activity and thermogenesis (computed as CAL EE--BMR and TEE--BMR) increased by only 0.9 +/- 0.4 and 0.9 +/- 2.1 MJ/d, respectively. All outcomes were consistent with theoretical changes due to the increased fat-free mass, body weight, and energy intake. There was no evidence of any active energy-dissipating mechanisms.

Carbohydrate balance and the regulation of day-to-day food intake in humans.

The hypothesis that carbohydrate stores are an important determinant of voluntary food intake was tested by covert dietary manipulation of carbohydrate stores in nine men during 2 d of continuous whole-body calorimetry that provided half-hourly monitoring of energy and fuel balance. On day 1 subjects were fed diets intended to maintain energy balance but containing carbohydrate at either 3% (depletion) or 47% (control) energy. Average carbohydrate balance changed by 153 +/- 42 g (mean +/- SD). Subsequent (day 2) ad libitum food intake from a normal diet of fixed macronutrient composition was identical on the control and depletion protocols: 12.73 +/- 2.24 and 12.72 +/- 2.01 MJ, respectively. The carbohydrate-depletion protocol caused a suppression of carbohydrate oxidation (174 +/- 41 vs 256 +/- 39 g, P < 0.001) and a reciprocal elevation in fat oxidation (120 +/- 11 vs 89 +/- 12 g, P < 0.001). These readjustments in fuel utilization were the primary mechanism for re-establishing carbohydrate balance. This study does not support the hypothesis that the need to maintain specific carbohydrate stores is a determinant of food intake in the short term.

In vivo measurement of changes in body composition: description of methods and their validation against 12-d continuous whole-body calorimetry.

The accuracy of a variety of in vivo body-composition techniques (densitometry, total body water, skinfold thicknesses, whole-body impedance and resistance, body mass index, and two three-compartment models) was assessed by comparison with fat balance. Three subjects were overfed and three underfed while confined to a 30-m3 whole-body calorimeter continuously for 12 d. Mean weight changes were +2.90 kg during overfeeding and -3.47 kg during underfeeding. The change in fat mass accounted for 37.1% during overfeeding and 59.3% during underfeeding. In comparison with energy and nitrogen balance, a three-compartment model yielded the least bias and greatest precision. The smallest change in fat mass that can be measured by such a method in an individual subject is 1.54 kg (2 SD). Of the prediction techniques considered, skinfold thicknesses or the body-mass-index formula appear to be more precise than estimates based on resistance or impedance.

Effects of dietary supplementation on work performance in Gambian laborers.

The effect of food supplementation on productivity of Gambian subsistence farmers was studied during a natural food shortage induced by the annual hungry season. Sixteen men in two groups matched for weight, height, hemoglobin, and physical-work capacity followed a crossover protocol with 6-wk supplementation and control periods. Productivity was assessed over the final 3 wk of each period by quantifying piece-rate-paid road building. Supplementation comprised an ad libitum supply of highly palatable energy-dense food provided three times daily. Outcome variables were total loads transported, loads per working hour, time per load, total energy expenditure assessed by doubly labeled water and heart-rate monitoring, postwork activity, and anthropometry. Body weight decreased during control periods, indicating a real energy deficit, and increased during supplementation in both groups. Supplementation had no significant impact on productivity variables. Energy-deficient men can maintain maximal productivity over short periods if sufficiently motivated but at the expense of body weight.

Energy expenditure from minute-by-minute heart-rate recording: comparison with indirect calorimetry.

Total daily energy expenditure (TDEE) and energy expended in activity (EAC) were estimated by the minute-by-minute heart-rate method in 22 (16 men, 6 women) individually calibrated subjects and compared with values obtained by whole-body indirect calorimetry. Subjects followed four activity protocols during the 22 h in the calorimeter; no exercise (n = 6) and 2 (n = 5), 4 (n = 4), and 6 (n = 6) 30-min bouts of exercise on a bicycle ergometer at varying intensities. There were no statistically significant differences between the two methods in TDEE or EAC in any of the sex or protocol groupings. The regression of TDEE by heart rate on TDEE in the calorimeter was y = 0.92x + 1.0 MJ; (r = 0.87, SEE = 0.91 MJ). The heart-rate method also follows the varying activity patterns of individuals and can be used to closely estimate the TDEE and EAC of even small (n = 4-6) groups of subjects. In the present measurements, it gave a maximum error of TDEE for individuals of +20% and -15%.

Effect of alcohol on postmeal fat storage.

Energy expenditure and macronutrient balances were assessed in normal healthy men by whole-body indirect calorimetry after meals consumed with and without ethanol to test the theory that alcohol energy is not fully available because of futile cycling. Alcohol addition (A) or isoenergetic substitution (S) caused fat retention by significantly suppressing its oxidation when the alcohol was actively metabolized (0-6h). However, on protocol S, fat balance was later reestablished due to raised fat oxidation (6-20.5 h) secondary to a relative carbohydrate deficiency. On protocol A, fat balance remained significantly raised. The thermogenic effect of alcohol was similar to that of carbohydrate, providing no evidence for futile cycling. Short-term studies that fail to account for later readjustments of macronutrient balance can be misleading. We conclude that alcohol has a fat-sparing effect similar to that of carbohydrate and will only cause fat gain when consumed in excess of normal energy needs.

Alterations in fuel selection and voluntary food intake in response to isoenergetic manipulation of glycogen stores in humans.

This study investigated the relative importance of alterations in carbohydrate intake or oxidation as mechanisms for rectifying extreme perturbations of glycogen stores. Six lean men were studied on three occasions in which a stabilization period (days 1 and 2) was immediately followed by whole-body indirect calorimetry (days 3-5). Glycogen stores were manipulated on days 3 and 4 by using isoenergetic diets providing carbohydrate at 79% (HC), 48% (MC), or 9% (LC) of energy. Free access to MC meals and snacks was allowed on days 5 and 6 outside the calorimeter. The manipulations caused large alterations in glycogen stores (HC, +206 g; MC, +132 g; LC, -121 g; HC vs LC, 327 g), but subsequent voluntary food intake was very similar across treatments (HC, 18.2 MJ/36 h; MC, 17.7 MJ/36 h; LC, 18.1 MJ/36 h, NS). Over days 3-5 the average difference in carbohydrate intake (HC vs LC) was 16.1 MJ (1010 g), but balances differed by only 1.7 MJ (110 g) because of autoregulatory changes in carbohydrate oxidation. These were the only significant mechanisms for reestablishing carbohydrate balance.

Longitudinal assessment of the components of energy balance in well-nourished lactating women.

The mechanisms by which well-nourished women meet the additional energy costs of lactation were studied by measuring energy intake (EI), basal metabolic rate (BMR), total energy expenditure by doubly labeled water (TEE), physical activity plus thermogenesis (TEE-BMR), changes in body fat stores, and milk energy transfer. Ten women were studied at 36 wk gestation; 4, 8, and 12 wk lactation (L4, L8, L12); and when nonpregnant and nonlactating (NPNL) after weaning. At L4, L8, and L12 the energy transferred in milk averaged 2245, 2225, and 2217 kJ/d with an additional 445 kj/d (106 kcal/d) estimated as being necessary for synthesis. EI was 1360, 1740, and 1275 kJ/d higher than the NPNL values, representing 56% of the costs of lactation. The remaining 44% was met by a reduction in TEE (-945, -688, and -826 kJ/d vs NPNL) caused largely by a reduction in physical activity because BMR was essentially unchanged (+29, -12, and -218 kJ/d). The energy-balancing strategies adopted by different women varied markedly.

Effects of weight cycling on body composition.

It is frequently claimed that weight cycling, or "yo-yo" dieting, causes an inappropriate and permanent loss of lean body mass (LBM). Data are presented from a rural African population that undergoes profound weight cycling caused by an annual hungry season. No detrimental effect on LBM was observed. Data are also presented from an 18-wk prospective study of moderately obese British women who underwent three cycles of VLCD-induced weight loss and subsequent relapse. The proportion of weight lost as LBM was no greater than predicted. A review of the published results from experimental weight cycling in small animals also shows a high level of consensus that cycling does not significantly alter body composition. We conclude that, although weight cycling may affect growth of young animals, metabolic efficiency, and health, these effects are not mediated through permanent alterations in body composition.

Longitudinal assessment of energy expenditure in pregnancy by the doubly labeled water method.

Twelve women were studied before pregnancy and at 6-wk intervals from 6 to 36 wk gestation. Total energy expenditure (TEE) by the doubly labeled water method, basal metabolic rate (BMR), energy intake, and body composition were assessed on each occasion. There was substantial interindividual variation in the response to pregnancy. Mean total energy costs were as follows: delta BMR 112 +/- 104 MJ (range -53 to 273), delta TEE 243 +/- 279 MJ (range -61 to 869 MJ), and fat deposition 132 +/- 127 MJ (range -99 to 280 MJ). The mean total cost of pregnancy (cumulative TEE above baseline+energy deposited as fat and as products of conception) was 418 +/- 348 MJ (range 34-1192 MJ). This was much higher than current recommendations for incremental energy intakes. Self-recorded incremental intakes (208 +/- 272 MJ) seriously underestimated the additional costs. The variability in response emphasizes the problems in making prescriptive recommendations for individual women, because there is no way of predicting metabolic or behavioral responses to pregnancy.

Changes in macronutrient balance during over- and underfeeding assessed by 12-d continuous whole-body calorimetry.

Alterations in energy balance must be accommodated by adjustments in the net storage of the major energy-yielding macronutrients: carbohydrate, protein, and fat. This study used continuous whole-body calorimetry to measure changes in energy expenditure and substrate oxidation during a 12-d imposed energy imbalance in six lean men on mixed diets (overfeeding: 16.5 MJ/d, +33%, n = 3; underfeeding: 3.5 MJ/d, -67%, n = 3). Changes in total energy expenditure (TEE) and its components were modest; TEE changed by +6.2% (overfeeding) and -10.5% (underfeeding). In consequence, body weight changed by +2.90 and -3.18 kg. Marked changes in metabolic fuel selection occurred over the course of the study. Carbohydrate intake (540 and 83 g/d for overfeeding and underfeeding, respectively) exerted direct autoregulatory feedback on carbohydrate oxidation (551 and 106 g/d at day 12 for overfeeding and underfeeding, respectively). Subjects were close to balance by day 5. Changes in protein oxidation were small and not sufficient to prevent the oxidation of body protein mass, or its accretion, in response to energy deficit or surplus. Fat oxidation (59 and 177 g/d for overfeeding and underfeeding, respectively) was not sensitive to dietary fat intake (150 and 20 g/d, for overfeeding and underfeeding, respectively), rather, its oxidation was inversely related to the oxidation of other substrates. Changes in fat balance accounted for 74.1% and 84.0% of the energy imbalance during overfeeding and underfeeding, respectively. This study shows a clear oxidative hierarchy for the macronutrients. Metabolic fuel selection is dominated by the need to maintain carbohydrate balance. This induces inappropriate counterregulatory alterations in fat oxidation during energy surplus.

Maternal and fetal determinants of adult diseases.

Recent epidemiologic studies in the United Kingdom have led to the hypothesis that adverse nutritional experiences in utero have a powerful influence on the development of degenerative diseases in adulthood. Poor fetal growth as measured by weight, length, head, chest, and abdominal circumferences is a strong predictor of hypertension, diabetes, hyperlipidemia, alteration in clotting factors, Syndrome X,* and mortality from cardiovascular and chronic obstructive airways disease. The theory of fetal origins of adult disease proposes that early defects in the development, structure, and function of organs lead to a programmed susceptibility, which interacts with later diet and environmental stresses to cause overt disease many decades after the original insult.

Measurements of total energy expenditure provide insights into the validity of dietary measurements of energy intake.

The quantification of errors inherent in methods of measuring dietary intake has been handicapped by the absence of independent markers for testing their validity. The doubly labeled water technique permits a precise measure of energy expenditure in free-living persons. Because energy expenditure must equal energy intake in populations in energy balance, this technique may be used to validate the assessment of energy intake. A series of studies demonstrated good agreement between mean energy intake and mean energy expenditure when food intake was recorded by observers or when it was self-reported by normal-weight, self-selected, highly motivated volunteer subjects using weighed records. However, in randomly recruited men and women, energy intake by weighed records was 82% and 81%, of energy expenditure, respectively, indicating underestimation of habitual intake. Men and women in the lowest third of reported intake recorded energy expenditure of only 69% and 61%, respectively. Reported intake of obese and previously obese women was only 73% and 64% of expenditure, whether measured by weighed record or by diet history, confirming suspicions that these subjects misrepresented their intake. Acceptable weighed records were obtained from 7- and 9-year-olds whereas 15- and 18-year-olds underestimated intake. Diet histories taken from the same children tended to overestimate intake. These studies suggest that, ideally, all dietary studies should include independent measures of validity.

Body mass index and lactation performance.

Data from the world literature have been analysed in order to test whether low body mass index (BMI: kg/m2) is a useful indicator of functional impairment of lactation performance. Forty-one databases containing 1726 measurements have been identified as having reliable estimates of breast-milk quantity and/or quality. There is no detectable relationship between maternal BMI and the volume of milk produced by mothers when analysed according to the mean BMI of different populations, or of different subgroups stratified by BMI within populations. This conclusion holds even at BMIs < 18.5. The most remarkable feature of the data is the very high milk volumes produced by very thin mothers. It is accepted that the composition of breast milk is relatively unaffected by general undernutrition of the type that would be indicated by a low BMI with the possible exception of milk fat levels and hence the energy content. Analysis of the available data reveals studies in which there are weak, but significant, correlations between maternal BMI and milk fat. However, other studies show no association or even a negative relationship. Inter-country analysis fails to reveal any detectable association between BMI and milk energy. Milk energy levels seem adequate even at BMIs < 18.5. It is concluded that human lactation performance is extremely robust and that BMI does not provide a useful indicator of function at the levels studied so far. Lactation performance must become compromised when undernutrition is sufficiently severe, but it appears that this must occur only in famine or near famine conditions.

Overnight and basal metabolic rates in men and women.

The FAO/WHO/UNU recommendations for energy requirements assume that the energy cost of sleep is equal to the basal metabolic rate (BMR). We have tested the validity of this assumption by analysing overnight and BMR measurements made by whole-body indirect calorimetry. Data from 80 healthy subjects measured on a total of 246 occasions have been used. In a subgroup of 40 normal lean subjects the mean ratio of overnight metabolic rate (Overnight MR): BMR was 0.95 (range 0.85 - 1.02, s.d. 0.04). The mean ratio of lowest sleeping metabolic rate (Lowest SMR): BMR was 0.88 (range 0.83 - 0.96, s.d. 0.04). Ratios of Overnight MR: BMR were not significantly affected by different levels of exercise on the preceding day. This ratio was significantly higher for subjects who were obese, late pregnant or attached to ECG electrodes. With the exception of the late pregnant subjects these groups had the same Lowest SMR:BMR ratios as the normal lean subjects, indicating that the higher Overnight MR was caused by disturbed sleep. The data suggest that the use of BMR to estimate overnight energy expenditure would introduce an average overestimate of approximately 5 per cent during the actual hours of sleep, but that when applied over 24 h the error becomes negligible.

Residual effect of graded levels of exercise on metabolic rate.

The hypothesis that exercise induces a residual effect on metabolic rate only when the intensity exceeds a certain threshold was tested by studying 10 healthy, untrained adults performing graded levels of bicycle ergometry on five separate occasions. The exercise consisted of four 30-min periods at intensities ranging from 0 to 100 Watts. Energy expenditure was measured by continuous indirect whole-body calorimetry. The highest level of exercise increased 24-h energy expenditure by 34 per cent. Food intake was modified for each measurement in order to maintain energy balance. Sleeping and basal metabolic rates on the night following exercise were raised even at low intensities of exercise. There was an almost linear dose-response relationship and no evidence of a threshold. However, the effect was small, amounting to only 5.8 per cent overnight and 3.9 per cent in the morning following 2 h exercise at over 60 per cent VO2 max during the preceding day. This suggests that the residual energy expenditure incurred after moderate levels of exercise is unlikely to be a very useful adjunct to slimming regimes.

Dose-response relationship between fat ingestion and oxidation: quantitative estimation using whole-body calorimetry and 13C isotope ratio mass spectrometry.

OBJECTIVE: To determine dose-dependent relationship between ingested fat and its oxidation in the immediate post-prandial period in humans. DESIGN: Subjects were randomly selected for the study at the Dunn Clinical Nutrition Centre, Cambridge, UK. Subjects ingested naturally enriched 13C corn-oil doses (range 20-140g) in a whole-body indirect calorimeter, and were studied for 8 h. Ingested fat oxidation was estimated from the subject's breath 13C enrichment and total carbon dioxide production. Total fat and carbohydrate oxidation were estimated from non-protein oxygen and carbon dioxide exchanges. Endogenous fat oxidation was estimated as the difference between total fat and ingested fat oxidation. RESULTS: The amount of fat dose oxidized was nonlinearly related to the amount ingested. On average, 25.6+/-2.7% of the mean fat dose was oxidized. A significant (r = - 0.72, P < 0.001) inverse correlation was found between the amount of fat dose and the proportion oxidized. Endogenous carbohydrate oxidation was negatively and significantly correlated to fat dose oxidized (r= -0.61, P < 0.01), but it was not correlated to endogenous fat oxidation. CONCLUSIONS: There was a nonlinear relationship between amount of fat dose and its quantity that was oxidized in the immediate post-prandial period. The inverse relationship between the size of the fat load and the proportion that was oxidized post-prandially implies increased dietary fat storage beyond about 50 g in a normal resting adult. This has important implications for 13CO2-based studies.

Critical evaluation of energy intake data using fundamental principles of energy physiology: 1. Derivation of cut-off limits to identify under-recording.

This paper uses fundamental principles of energy physiology to define minimum cut-off limits for energy intake below which a person of a given sex, age and body weight could not live a normal life-style. These have been derived from whole-body calorimeter and doubly-labelled water measurements in a wide range of healthy adults after due statistical allowance for intra- and interindividual variance. The tabulated cut-off limits, which depend on sample size and duration of measurements, identify minimum plausible levels of energy expenditure expressed as a multiple of basal metabolic rate (BMR). CUT-OFF 1 tests whether reported energy intake measurements can be representative of long-term habitual intake. It is set at 1.35 x BMR for cases where BMR has been measured rather than predicted. CUT-OFF 2 tests whether reported energy intakes are a plausible measure of the food consumed during the actual measurement period, and is always more liberal than CUT-OFF 1 since it has to allow for the known measurement imprecision arising from the high level of day-to-day variability in food intake. The cut-off limits can be used to evaluate energy intake data. Results falling below these limits must be recognized as being incompatible with long-term maintenance of energy balance and therefore with long-term survival.