A stable isotope method for the simultaneous measurement of vitamin K1 (phylloquinone) kinetics and absorption.

OBJECTIVES: To measure uptake and disposal kinetics and absolute absorption of vitamin K(1) using two stable isotope-labelled forms of vitamin K(1). SUBJECTS: Ten subjects (nine women and one man) aged between 22 and 31 years, with a mean (+/-standard deviation) body mass index of 22.5+/-2.4 kg/m(2). Subjects took capsules containing 3 microg of methyl-(13)C vitamin K(1), three times a day for six days to reach a steady state for plasma vitamin K(1) isotopic enrichment. On day seven, subjects were given an intravenous dose of Konakion MM to measure disposal kinetics and at the same time, a capsule containing 4 microg of ring-D(4) vitamin K(1) to measure absorption. Plasma vitamin K(1) concentration was measured by high-performance liquid chromatography and isotopic composition by gas chromatography mass spectrometry. RESULTS: The disposal kinetics of the intravenous dose of vitamin K(1) were resolved into two exponentials with half-times of 0.22 (+/-0.14) and 2.66 (+/-1.69) h. Absorption of oral, deuterated vitamin K(1) was 13 (+/-9)%. CONCLUSIONS: Two-compartmental kinetic parameters observed in this study are similar to those obtained previously using radioactive tracers, but there may be additional slow-turnover body pools acting as stores of vitamin K(1). The kinetic parameters determined from the intravenous dose allowed determination of the absolute absorption of vitamin K(1) from a bolus oral dose.

Human milk vacuolating cytotoxin A immunoglobulin A antibodies modify Helicobacter pylori infection in Gambian children.

We collected data, including the weights, urea breath test results, and presence of maternal milk cytotoxin-associated gene-specific and vacuolating cytotoxin A-specific immunoglobulin A monthly from 48 mothers and infants (to 44 weeks of age) in The Gambia. In all, 11 children (23%) had negative urea breath test results, and 37 (77%) had positive results. Weight loss associated with Helicobacter pylori colonization was restricted to children whose mothers did not produce anti-vacuolating cytotoxin A antibodies in their milk (P=.028, by t test).

2H2O turnover method as a means to detect bias in estimations of intake of nonbreast milk liquids in breast-fed infants.

OBJECTIVE: Firstly, to compare food, and macronutrient intake as obtained from a single 24-h recall and a frequency questionnaire (FQ) covering a 14-day period in breast-fed infants aged 4 months of age. Secondly, nonbreast milk water intake (NB-WI, ml/day) was used as an estimation of energy and macronutrient intake, and NB-WI as calculated from FQ (NB-WIFQ) was compared with NB-WI as measured using the dose-to-the-mother 2H2O turnover method (NB-WIDO) covering the same 14-day period. DESIGN: Cross-sectional. SETTING: Community-based study in urban Pelotas, Southern Brazil. SUBJECTS: In all, 67 breast-fed infants aged 4 months of age recruited at birth. MAIN OUTCOME MEASURES: (1) Bias in estimations of food and macronutrient intake of the 24-h recall relative to FQ; (2) Bias in NB-WIFQ relative to NB-WIDO. RESULTS: In infants with an energy intakeFQ from complementary foods above the 50th percentile (1.03 kcal/day), estimations of water, tea, juice, and milk intake were not different between 24-h recall and FQ (n=34). Nor were estimations of energy and macronutrient intake (protein, fat, and carbohydrates) different between the two methods, and bias was nonsignificant. NB-WIDO was divided into quintiles and compared with NB-WI(FQ). The first two quintiles included negative values for NB-WIDO as a result of random errors of the 2H2O turnover method. Subsequently, bias of NB-WIFQ relative to NB-WIDO was positive in the 1st (P=0.001) and 2nd quintile (P=0.638), respectively. Bias was negative for the three highest quintiles, and within this group, underestimation by FQ was significant for the 3rd and 4th quintile (-57.4%, P=0.019; -43.7%, P=0.019). CONCLUSIONS: Firstly, at the age of 4 months FQ covering a 14-day period provides similar results on food and macronutrient intake as compared to a single 24-h recall for estimations of complementary liquid foods. Secondly, NB-WIFQ appeared to be a good proxy for macronutrient and energy intake in breast-fed infants receiving other liquids. In infants with NB-WIDO>0, the method provides a useful tool for the detection of bias from FQ, and results indicate an underestimation from FQ relative to the 2H2O turnover method. This exercise could be applied wherever the 2H2O turnover method is used in combination with conventional food consumption techniques for measuring intake of nonbreast milk liquids of breast-fed infants in whom solid foods have not yet been introduced. It would help interpreting estimations of macronutrient intake, and could be relevant to studies of dietary intake of infants and its relationship with growth and health.

Contributions of the doubly labeled water method to studies of energy balance in the Third World.

Of >250 studies on energy metabolism using the doubly labeled water (DLW) technique, approximately 12 full papers describe work performed in the Third World. Unfortunately, the term "Third World" is imprecise and the focuses of individual studies were too varied to allow much comparison among the data. There is a need to develop a more uniform approach. Useful investigations will allow comparisons of energy metabolism to be made in a consistent way across a variety of socioeconomic groups within the same country, and between the Third World and the developed world, with a commitment to the long term. In this way, the DLW method, if combined with other measurements of activity, energy intake, and body composition, will provide useful information on energy requirements and the consequences of inadequate or excessive energy intakes for the individual. Such investigations should be done, with standard protocols where possible, not just for the DLW method but also for those methods with which DLW should be integrated. Only if these suggestions are followed will real "value for money" be obtained from DLW studies in the Third World or elsewhere. In the context of these criteria, studies in the Third World using the DLW method have been only partly successful.

Energy expenditure of young Polynesian and European women in New Zealand and relations to body composition.

BACKGROUND: Reduced energy expenditure and excessive energy intake have been hypothesized to cause obesity. New Zealanders of Polynesian origin have a higher prevalence of obesity than do those of European origin. OBJECTIVE: We investigated relations between components of energy expenditure and body composition. DESIGN: We measured total energy expenditure (TEE) and resting metabolic rate (RMR) in 80 young women [40 New Zealand (NZ) Polynesian and 40 NZ European] aged 18-27 y by the doubly labeled water method and indirect calorimetry, respectively. Each group was partitioned into nonobese and obese on the basis of percentage body fat. RESULTS: TEE and body weight were highly correlated in nonobese NZ Europeans (n = 23, r = 0.76, P < 0.001), obese NZ Europeans (r = 0.58, P = 0.016), and nonobese NZ Polynesians (n = 25, r = 0.59, P = 0.002) but not in obese NZ Polynesians (r = 0.11, P = 0.70). Activity energy expenditure (AEE = TEE - RMR) was similar in obese Polynesians and Europeans (mean+/-SD: 5.5+/-2.2 and 5.2+/-1.9 MJ/d, respectively), but significantly higher in nonobese Polynesians (5.7+/-2.5 MJ/d) than in their European counterparts (3.8+/-1.9 MJ/d, P = 0.005). Similar trends were seen when AEE adjusted for body weight and TEE/RMR were compared among the subgroups. Body weight and RMR together accounted for 66% of the variation in TEE for the European group but only 17% for the Polynesian group. CONCLUSION: Care should be taken in applying "Caucasian norms" relating to energy expenditure to NZ Polynesian people.

Lactational performance in relation to energy intake in the baboon.

The relationship between energy intake and lactational performance in the baboon was investigated by determining energy intake, milk output and energy balance in animals fed ad libitum during a nonreproductive phase and during lactation, or fed 80% or 60% of ad libitum intake during lactation. No evidence was found for an increased efficiency of energy utilization during lactation when feeding was ad libitum, as judged by calculated energy used on activity and maintenance. Restricted feeding did however produce an increase in efficiency, estimated at 17-25%. This change enabled milk output and body nutrient stores to be protected when the restriction was to 80% of the ad libitum intake but at 60% of ad libitum intake, milk output was reduced and body nutrient mobilization was increased. It is proposed that low maternal food intake is associated with impairment of lactational performance when it is also severe enough to increase body nutrient mobilization.

Energy expenditure determined by the doubly labeled water method in Bolivian Aymara living in a high altitude agropastoral community.

Using the doubly labeled water method (DLW), we determined total energy expenditure (TEE) under free-living conditions in 23 rural Bolivian Aymara (males and females aged 4-65), natives of a small, high-altitude (4000-4100 m), rural agropastoral community in the Andes mountains. In the adults (18-65 y of age), mean TEEs for males and females were 11.1 +/- 1.8 MJ/24 h (range: 9.3-14.1) and 9.8 +/- 0.9 MJ/24 h (8.8-11.3). Non basal energy expenditure expressed as TEE relative to basal energy expenditure (TEE:RMR) and as the difference between TEE and RMR per unit of weight [(TEE-RMR)/wt] showed no significant sex differences. TEE:RMR in the adults (2.00 +/- 0.21) was significantly greater (P < 0.05) than that of adolescents and children (1.67 +/- 0.25), but the mean (TEE-RMR)/wt values were similar in children, adolescents, and adults. Significantly high RMR:FFM values in children and adolescents, reflecting a curvilinear relation of RMR and FFM, have enlarged the differences in TEE:RMR by age groups. When compared with other DLW studies for free-living nonobese adults, the RMR of adult Aymara subjects normalized by the ratio method (RMR:FFM) and by the regression-based method (RMR adjusted with FFM as the covariate) was not significantly different from that observed in subjects living in low altitudes. As compared to FAO/WHO/UNU (1985) recommendations, activity levels were classified as heavy for the adult females and moderate-heavy for the adult males. Energy requirements for maintaining everyday tasks in the Andean people are much higher than expected from the previous studies on food consumption.

Covert manipulation of the ratio of dietary fat to carbohydrate and energy density: effect on food intake and energy balance in free-living men eating ad libitum.

We previously increased the energy density and fat content across three diets (factorial design), which led to a marked increase in energy intake in six men over 7 d while continuously resident in a whole-body indirect calorimeter. In the present study we fed the same diets to seven men who were resident in, but not confined to, a metabolic suite for 2 wk/diet. This added a component of increased physical activity. The fat, carbohydrate, and protein contents, respectively, of each diet (as a percent of energy) were as follows: low-fat (LF), 20:67:13; medium-fat (MF), 40:47:13; and high-fat (HF), 60:27:13. Energy density increased as the percent of fat in the diet increased. Energy intakes from the LF, MF, and HF diets (9.11, 10.32, and 12.78 MJ/d, respectively) were almost identical to those in our calorimeter study (9.02, 10.2, and 12.35 MJ/d, respectively) whereas energy expenditures (estimated by the doubly labeled water method) were 12.45, 12.10, and 11.97 MJ/d on the LF, MF and HF diets, respectively, compared with 9.48, 9.53, and 9.78 MJ/d, respectively, in our calorimeter study. This finding suggests that diet composition and energy expenditure combined influence energy balance in humans.

Fat gain during pregnancy in rural African women: the effect of season and dietary status.

Body-fat gain during pregnancy (weight--total body water/0.73) was measured in 50 rural Gambian women exposed to seasonal energy demands of subsistence farming and to annual preharvest food shortages. Twenty-eight women received dietary supplements in amounts previously shown to increase birth weight. In unsupplemented women, fat gain was profoundly affected by the seasons through which the pregnancy progressed, ranging from an estimated loss of 4.7 kg to a net gain of 3 kg at various times of the year. Adjustment for season revealed, however, that pregnancy per se was without effect on body fat content. Supplementation increased fat gain during pregnancy by approximately 2 kg (p less than 0.05) and gave protection against the worst effects of season on energy balance. These findings contribute to our understanding of the consequences of low food intake during pregnancy and the effects of dietary supplementation on birth weight.

PIP: Body fat gain during pregnancy (weight-total body water/0.73) was measured in 50 rural Gambian women exposed to seasonal energy demands of subsistence farming and to annual preharvest food shortages. 28 women received dietary supplements in amounts previously shown to increase birth weight. In unsupplemented women, fat gain was profoundly affected by the seasons through which the pregnancy progressed, ranging from an estimated loss of 4.7 kg to a net gain of 3 kg at various times of the year. Adjustment for season revealed, however, that pregnancy per se was without effect on body fat content. Supplementation increased fat gain during pregnancy by about 2 kg (p0.05) and gave protection against the worst effects of season on energy balance. These findings contribute to our understanding of 1) the consequences of low food intake during pregnancy and 2) the effects of dietary supplementation on birth weight.

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.

Comparison of the doubly labeled water (2H2(18)O) method with indirect calorimetry and a nutrient-balance study for simultaneous determination of energy expenditure, water intake, and metabolizable energy intake in preterm infants.

The doubly labeled water method was compared with indirect calorimetry and a nutrient-balance study for simultaneous determination of rates of CO2 production, energy expenditure, and water intake over 5 days in four preterm infants. Additionally, metabolizable energy (ME) intake estimated using the isotope procedure (as energy expenditure plus an estimate for energy deposition based on weight gain), was compared to ME intake measured in the balance study. Compared to values obtained by traditional methods, calculated CO2 production, energy expenditure, and water intake differed by -1.4 +/- 4.8% (SD), +0.3 +/- 2.6%, and +5.7 +/- 1.4%, respectively; the difference in water intake was significant (p less than 0.05). Calculated ME intakes were 5.3 +/- 19.3% less than measured intakes, but the difference was not significant. These findings indicate that the doubly labeled water method can provide accurate information on rates of CO2 production, energy expenditure, and water intake in preterm infants, but individual estimates of ME intake may be subject to substantial error.

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 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.

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.

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.

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.

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.

Energy expenditure of stunted and nonstunted boys and girls living in the shantytowns of São Paulo, Brazil.

BACKGROUND: Stunting increases the risk of obesity in developing countries, particularly in girls and women, but the underlying reason is not known. OBJECTIVE: Our objective was to test the hypothesis that stunted children have lower energy expenditure than do nonstunted children, a factor that has predicted an increased risk of obesity in other high-risk populations. DESIGN: A cross-sectional study was conducted in shantytown children from São Paulo, Brazil. Twenty-eight stunted children aged 8-11 y were compared with 30 nonstunted children with similar weight-for-height. Free-living total energy expenditure (TEE) was measured over 7 d by using the doubly labeled water method. In addition, resting energy expenditure (REE) was measured by indirect calorimetry and body composition was measured by dual-energy X-ray absorptiometry. RESULTS: There were no significant associations between stunting and any measured energy expenditure parameter, including REE adjusted for weight (f1.gif" BORDER="0"> +/- SEM: 4575 +/- 95 compared with 4742 +/- 91 kJ/d, in stunted and nonstunted children, respectively) and TEE adjusted for weight (8424 +/- 239 compared with 8009 +/- 221 kJ/d, in stunted and nonstunted children, respectively). In multiple regression models that included fat-free mass and fat mass, girls had significantly lower TEE than did boys (P: < 0.05) but not significantly lower REE (P: = 0.17). CONCLUSIONS: There was no association between stunting and energy expenditure after differences between groups in body size and composition were accounted for. However, the girls had lower TEE than did boys, which may help to explain the particularly high risk of obesity in stunted adolescent girls and women in urban areas of developing countries.

De novo lipogenesis during controlled overfeeding with sucrose or glucose in lean and obese women.

BACKGROUND: The results of previous studies suggest that de novo lipogenesis may play an important role in the etiology of obesity, particularly during overconsumption of different carbohydrates. OBJECTIVE: We hypothesized that de novo lipogenesis would increase during overfeeding, would vary depending on the type of carbohydrate consumed, and would be greater in obese than in lean women. DESIGN: De novo lipogenesis was measured during 96 h of overfeeding by 50% with either sucrose or glucose and during an energy balance treatment (control) in 8 lean and 5 obese women. De novo lipogenesis was determined by measuring the amount of deuterium incorporation into plasma triacylglycerols. Fat and carbohydrate balance were measured simultaneously by continuous whole-body calorimetry. RESULTS: De novo lipogenesis did not differ significantly between lean and obese subjects, except with the control treatment, for which de novo lipogenesis was greater in the obese subjects. De novo lipogenesis was 2- to 3-fold higher after overfeeding by 50% than after the control treatment in all subjects. The type of carbohydrate overfeeding (sucrose or glucose) had no significant effect on de novo lipogenesis in either subject group. Estimated amounts of absolute VLDL production ranged from a minimum of 2 g/d (control) to a maximum of 10 g/d after overfeeding. This compares with a mean fat balance of approximately 275 g after 96 h of overfeeding. Individual subjects showed characteristic amounts of de novo lipogenesis, suggesting constitutive (possibly genetic) differences. CONCLUSION: De novo lipogenesis increases after overfeeding with glucose and sucrose to the same extent in lean and obese women but does not contribute greatly to total fat balance.

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.