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Background: Malnutrition in late infancy in developing countries may result from poor-quality complementary foods that displace breast milk. Objective: The objective of the study was to assess the effects of fortified complementary blends of different energy densities on growth, hemoglobin concentrations, and breast milk intake of 9-mo-old Zambian infants. Design: Infants were randomly assigned at 6 mo of age to receive for 3 mo a fortified blend of maize, beans, bambaranuts, and groundnuts [Chilenje Baby Mix (CBM); energy density: 68 kcal/100 g; n = 37] or a similar blend with [alpha]-amylase (CBMA; energy density: 106 kcal/100 g; n = 44). Cross-sectional data were obtained at 9 mo for a control group of infants (n = 69) not given the diets. Breast milk intake was measured by using the dose-to-the-mother deuterium dilution technique. Results: No differences in weight or length z scores, all of which were within normal ranges, were seen between groups at 9 mo. Percentage fat mass was significantly (P = 0.01) greater in the infants in both the CBM (23.2 [+ or -] 2.7%) and CBMA (23.4 [+ or -] 2.5%) groups than in the control group (21.6 [+ or -] 2.6%). Hemoglobin concentrations were significantly (P = 0.03) greater in both intervention groups (CBM group: 104 [+ or -] 12 g/L: CBMA group: 103 [+ or -] 12 g/L) than in the control group (98 [+ or -] 14 g/L). Breast milk intake was not significantly (P = 0.87) different between groups (CBM group: 614 [+ or -] 271 g/d; CBMA group: 635 [+ or -] 193 g/d; control group: 653 [+ or -] 221 g/d). Conclusions: The study foods improved hemoglobin concentrations without reducing breast milk intake and may be used to improve the nutritional status of infants in developing countries. KEY WORDS Complementary food, micronutrient-fortified foods, [alpha]-amylase, infant growth, hemoglobin, breast milk intake, deuterium dilution, Zambia

Background: To support age-appropriate growth and to prevent and treat malnutrition in children with cystic fibrosis (CF), energy requirements for those children are often set above the requirements for healthy children. Care providers use one of several empirically derived formulas to calculate energy requirements, yet the validity of these formulas has seldom been tested. Objective: We evaluated 6 proposed formulas for calculating energy requirements in children with CF against a total energy requirement for children with CF (TER-CF) derived from measured total energy expenditure, fecal fat energy loss, and the theoretic energy required for age-appropriate tissue accretion. Design: Subjects were children aged 6-8 y who had CF and pancreatic insufficiency. Calculated TERs from each formula were evaluated against TER-CF by using summary statistics, regression analysis, and residual plots. Results: Subjects (n = 53) had suboptimal nutrition and growth status and mild-to-moderate lung disease. The formula that most closely (within 2%) approximated TER-CF was the estimated energy requirement (EER) formula at the active level (EE[R.sub.act]). Regression analysis of TER-CF onto calculated TER from each formula yielded the best indexes of model fit for the EE[R.sub.act] formula; residual plots of the EE[R.sub.act] formula were tightly and normally distributed around zero. Conclusions: The EE[R.sub.act] formula should be used to establish TER-CF in children in this age group who have mild-to-moderate CF. Changes in weight, height, and other indicators of nutritional status must be monitored to modify TER-CF as needed to support individual patient care goals. KEY WORDS Doubly labeled water, validation, energy expenditure, energy requirement, cystic fibrosis

Background: About 25-40% of hospital patients are malnourished. With current clinical practices, only 50% of malnourished patients are identified by the medical and nursing staff. Objective: The objective of this study was to report the cost and effectiveness of early recognition and treatment of malnourished hospital patients with the use of the Short Nutritional Assessment Questionnaire (SNAQ). Design: The intervention group consisted of 297 patients who were admitted to 2 mixed medical and surgical wards and who received both malnutrition screening at admission and standardized nutritional care. The control group consisted of a comparable group of 291 patients who received the usual hospital clinical care. Outcome measures were weight change, use of supplemental drinks, use of tube feeding, use of parenteral nutrition and in-between meals, number of consultations by the hospital dietitian, and length of hospital stay. Results: The recognition of malnutrition improved from 50% to 80% with the use of the SNAQ malnutrition screening tool during admission to the hospital. The standardized nutritional care protocol added [approximately equal to] 600 kcal and 12 g protein to the daily intake of malnourished patients. Early screening and treatment of malnourished patients reduced the length of hospital stay in malnourished patients with low handgrip strength (ie, frail patients). To shorten the mean length of hospital stay by 1 d for all malnourished patients, a mean investment of [euro] 76 (US$91) in nutritional screening and treatment was needed. The incremental costs were comparably low in the whole group and in the subgroup of malnourished patients with low handgrip strength. Conclusions: Screening with the SNAQ and early standardized nutritional care improves the recognition of malnourished patients and provides the opportunity to start treatment at an early stage of hospitalization. The additional costs of early nutritional care are low, especially in frail malnourished patients. KEY WORDS Malnutrition, hospital, Short Nutritional Assessment Questionnaire (SNAQ), screening, undernutrition, effectiveness, cost-effectiveness, length of hospital stay

Background: We showed previously that the activity of complex I (the first enzyme of the electron transport chain) in peripheral blood mononuclear cells decreases with malnutrition and increases to a subnormal value after 1 wk of refeeding, but the traditional markers of nutritional status do not do so. Objective: The aim of this study was to ascertain whether a period of nutritional intervention longer than 1 wk would normalize complex I activity and traditional markers of nutritional status. Design: Fifteen malnourished patients (7 women and 8 men) with [greater than or equal to] 10% body weight loss over the previous 6 mo were studied on the day of their admission to hospital and 7, 14 and 30 d after the beginning of nutritional support. Complex I activity in peripheral blood mononuclear cells, weight, height, body composition, body water compartments, dietary intake, and serum albumin concentrations were measured on each occasion. The results before and during nutritional intervention were compared with values obtained in 30 healthy volunteers (17 women and 13 men). Results: Complex I activity increased significantly after the first week of refeeding (P < 0.001) and reached a normal value after 1 mo of nutritional supplementation. Among the classic markers of nutritional status, only the ratio of extracellular water to intracellular water tended to decrease over the refeeding period. Conclusion: Complex I activity increases rapidly and is normalized by refeeding at a time when other markers of nutritional status do not change significantly. KEY WORDS Malnutrition, refeeding, peripheral blood mononuclear cells, mitochondria, complex I

Background: Children with severe edematous malnutrition have higher than normal oxidant damage and lower concentrations of the antioxidant reduced glutathione (GSH), which are associated with slower synthesis of GSH and with low extra- and intracellular concentrations of the precursor amino acid cysteine. Objective: We tested whether early dietary supplementation with cysteine could restore a normal GSH concentration and synthesis rate in these children. Design: Erythrocyte cysteine and GSH concentrations and the fractional and absolute synthesis rates of GSH were measured in 2 groups of 16 edematous malnourished children, 10 boys and 6 girls aged 6-18 mo, at 3 times after hospital admission: at [approximately equal to] 2 d (period 1), when they were malnourished and infected; at [approximately equal to] 11 d (period 2), when they were malnourished but cleared of infection; and at [approximately equal to] 50 d (period 3), when they had recovered. Supplementation with either 0.5 mmol * [kg.sup.-1] * [d.sup.-1] N-acetylcysteine (NAC group) or alanine (control group) started immediately after period 1 and continued until recovery. Results: From period 1 to period 2 the concentration and the absolute synthesis rate of GSH increased significantly (P < 0.05) in the NAC group but not in the control group. The increases in the GSH concentration and synthesis rate were [approximately equal to] 150% and 510% greater, respectively, in the NAC group than in the control group. The increases in the NAC group were associated with a significant effect of supplement (P < 0.03) on erythrocyte cysteine concentration. Conclusion: These results suggest that the GSH synthesis rate and concentration can be restored during the early phase of treatment if patients are supplemented with cysteine. KEY WORDS Glutathione, severe malnutrition, cysteine, edema, oxidant damage, children

The effect of starvation-related malnutrition on muscle performance and on the energy cost of exercise remains unknown, as does the timing of improvement by refeeding. Indeed, in most diseases that induce malnutrition, muscle dysfunction is worsened by an inflammatory process. Thus, physical performance and the energy cost of exercise were studied in 15 semistarvated malnourished anorexia nervosa (AN) patients during exercise on an ergometric bicycle (3-min steps of 30 W) before and after 8, 30, and 45 d of refeeding. Results were compared with those of 15 normal-weight healthy subjects matched for age, sex, and physical activity. Before refeeding, the workload reached during the exercise was 49% lower in AN patients than in control subjects (P [is less than] 0.01). It was correlated with body weight, fat-free mass, and leg muscle circumference (P [is less than] 0.002). The performance improved dramatically during refeeding (P [is less than] 0.03), reaching normal values after 45 d of refeeding, despite fat-free mass and leg muscle circumference values that were still 20% lower in AN patients than in control subjects (P [is less than] 0.01). At this time, the exercise-related [VO.sub.2] remained unchanged, being [is nearly equal to] 25% lower than that of the control subjects when corrected for muscle mass differences (P [is less than] 0.03). In conclusion, in AN patients muscle performance was restored by refeeding long before the patients achieved normal nutritional status. The economic cost of physical activity for these malnourished patients allows them to maintain a relatively high level of physical activity. This relative overactivity has two goals in AN: it reinforces anorexia and contributes to the excess of energy expenditure needed for weight loss.

The magnitude of metabolic adaptation to malnutrition is still debated and few studies have investigated the phase of recovery from malnutrition. The aim of the present work was to determine whether refeeding was associated with adaptive changes in 1) energy expenditure, 2) maximal capacity for oxidizing lipids, and 3) whole-body protein turnover. Eleven malnourished patients with nonneoplastic gastrointestinal diseases were studied by using indirect calorimetry and L-[1-[sup.13.C]leucine infusion while being infused with lipid-rich total parenteral nutrition (TPN). The same study was performed before initiation of TPN and after a mean gain of 6.5 kg body wt. In absolute values, resting energy expenditure (REE) increased after refeeding (4.05 [+ or -] 0.85 compared with 4.60 [+ or -] 1.05 MJ/d). Change in REE adjusted for fat-free mass (FFM) correlated significantly with change in body weight (r = 0.850, P = 0.01) and change in body fat (r = 0.798, P = 0.01) but not with change in FFM (r = -0.06, NS). Lipid oxidation decreased significantly after body weight gain (0.93 [+ or -] 0.28 compared with 0.50 [+ or -] 0.37 mg [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1]). When expressed per kg FFM, protein turnover and breakdown increased significantly during body weight gain. Moreover, the change in protein turnover correlated with the rate of change in FFM, suggesting that FFM accretion requires increased interorgan exchange of amino acids. Our data suggest that in patients similar to those studied here and during recovery from malnutrition, the degree of change in adjusted REE during refeeding is correlated with change in fat mass and not with change in FFM, and that there is a decrease in oxidation of infused lipids. These mechanisms may contribute to body fat repletion and regulation during weight gain.

It is valuable to be able to measure the body composition of malnourished (undernourished) patients and to monitor their response to refeeding. The use of direct measurements, such as total body water, extracellular water, and total body potassium for clinical monitoring is expensive and cumbersome. We therefore have developed predictive equations for these variables by using fixed-frequency bioelectrical impedance analysis (BIA). Our equations deliberately do not include weight because they are used to predict changes in body composition in patients who are gaining weight during refeeding. BIA could predict changes in body composition with significantly greater precision than anthropometry alone. We conclude that BIA can be used to monitor changes in body composition in patients during refeeding.

Malnutrition is very common in rural Africa, and previous studies have shown that many Africans have primary hypolactasia. People with this condition produce abnormally low amounts of an enzyme called lactase. Lactase is the enzyme that is responsible for digesting the lactose (sugar) present in milk. People who do not have enough of this enzyme cannot digest milk, and thus they can have severe diarrhea if they drink any milk or too much milk, depending on the amount of lactase they produce. (Another term for hypolactasia is lactose intolerance.) Therefore, this raises the question, is milk appropriate for treating malnourished African patients? In an attempt to answer this question, a study was done with 50 malnourished rural African patients who had hypolactasia. The subjects were treated with either whole milk, acidified milk (which contains half as much lactose as whole milk), or a diet without any lactose (lactose-free diet). The diets were administered to the patients through a nasogastric tube (a tube inserted into the nose that goes to the stomach). During the first two days of treatment, mild diarrhea occurred in 37 percent of the patients treated with acidified milk, in 54 percent of those on the lactose-free diet, and in 63 percent of those on the whole milk diet. Another 22 percent of the patients receiving the whole milk diet had to discontinue the diet because of severe diarrhea, while no patients on the lactose-free diet developed severe diarrhea. It is concluded that whole milk is not well tolerated in malnourished African patients with hypolactasia; acidified milk may be useful for these patients, however. (Consumer Summary produced by Reliance Medical Information, Inc.)

The role of nutritional support in clinical care has burgeoned over the past 40 y. Initially, total parenteral nutrition (TPN) was considered to be the standard of care. Later, the concept that enteral nutrition (EN) promoted gut function and prevented the translocation of intestinal bacteria resulted in EN becoming the standard of care. Furthermore, TPN was considered to be a dangerous form of therapy. Critical review of the data suggests that, in humans, TPN does not cause mucosal atrophy or increase bacterial translocation. Increased sepsis with TPN can be ascribed to overfeeding; the dangers of TPN-induced complications have been exaggerated. TPN is an equally effective alternative to EN when a risk of malnutrition is present and EN is not tolerated or when gut failure is present. Am J Clin Nutr 2001;74:160-3. KEY WORDS Total parenteral nutrition, enteral nutrition, TPN, EN, nutritional support, malnutrition, review

Protein-energy malnutrition (PEM) is common in connection with chronic disease and is associated with increased morbidity and mortality. Because the risk of PEM is related to the degree of illness, the causal connections between malnutrition and a poorer prognosis are complex. It cannot automatically be inferred that nutritional support will improve the clinical course of patients with wasting disorders. We reviewed studies of the treatment of PEM in cases of chronic obstructive pulmonary disease, chronic heart failure, stroke, dementia, rehabilitation after hip fracture, chronic renal failure, rheumatoid arthritis, and multiple disorders in the elderly. Several methodologic problems are associated with nutrition treatment studies in chronically ill patients. These problems include no generally accepted definition of PEM, uncertain patient compliance with supplementation, and a wide range of outcome variables. Available treatment studies indicate that dietary supplements, either alone or in combination with hormonal treatment, may have positive effects when given to patients with manifest PEM or to patients at risk of developing PEM. In chronic obstructive pulmonary disease, nutritional treatment may improve respiratory function. Nutritional therapy of elderly women after hip fractures may speed up the rehabilitation process. When administered to elderly patients with multiple disorders, diet therapy may improve functional capacity. The data regarding nutritional treatment of the conditions mentioned above is still inconclusive. There is still a great need for randomized controlled long-term studies of the effects of defined nutritional intervention programs in chronically ill and frail elderly with a focus on determining clinically relevant outcomes. Am J Clin Nutr 2001;74:6-24. KEY WORDS Protein-energy malnutrition, chronic obstructive pulmonary disease, chronic heart failure, stroke, dementia, hip fracture, chronic renal failure, rheumatoid arthritis, elderly, nutritional support

Background: Previous studies suggested that cell energetics are altered by malnutrition. Objective: We hypothesized that nutritional manipulations influence mitochondrial enzyme activities of the electron transport chain in both skeletal muscle and blood mononuclear cells. Design: After a gastrostomy tube was inserted, 44 rats were randomly assigned to 1 of 4 experimental groups: control fed (CF; 364 kJ/d for 7 d), hypoenergetic fed (HF; 92 kJ/d for 7 d), hypoenergetic protein refed (HPR; 92 kJ/d for 7 d and then 129 kJ/d for 1 d), and hypoenergetic glucose refed (HGR; 92 kJ/d for 7 d and then 129 kJ/d for 1 d). The protein and glucose contents of the liquid formulas were different for the HPR and HGR groups. After mitochondria were isolated from the soleus muscle, the activities of complexes I-IV were measured spectrophotometrically. Because of the lack of available tissue, only the activity of complex I was measured in the mononuclear cell extract. Results: The recovery of complex activities in the CF and HF groups was not significantly different in the mitochondrial fraction of the soleus muscle. Compared with that in the CF group, the activities of complexes I-III in the mitochondrial fraction of the soleus muscle and the activity of complex I in mononuclear cells were significantly lower in the HF group. The activities of complexes I-III in the mitochondrial fraction of the soleus muscle and the activity of complex I in mononuclear cells were significantly higher in the HPR than in the HF group. The activity of complex IV was generally not affected by nutritional manipulations. Conclusion: Malnutrition decreases activities of mitochondrial complexes, which are restored by protein but not glucose refeeding. Am J Clin Nutr 2001;73:975-83. KEY WORDS Protein-energy restriction, malnutrition, refeeding, mitochondrial complexes I-IV, electron transport chain, rats

Background: An increase in protein intake exerts a stimulating effect on protein kinetics in children, young adults, and healthy elderly persons. However, there are few data on the response to such dietary changes in malnourished elderly subjects, despite important medical implications in this population. Objective: The objective of this study was to determine the metabolic response to short-term nutritional supplementation in moderately malnourished elderly subjects. Design: The influence of 10 d of supplementation (1.67 MJ/d and 30 g protein/d) on body composition, resting energy expenditure, and whole-body protein kinetics was studied in 17 malnourished elderly patients and 12 healthy young adults. A control group of 6 malnourished elderly patients received no supplementation. Results: Supplemented elderly subjects had a significantly greater fat-free mass gain than did unsupplemented elderly subjects (1.3 and 0.1 kg, respectively; age effect, P [is less than] 0.05; diet effect, P [is less than] 0.02) and a significantly greater increase in fasting rate of protein synthesis than did young supplemented subjects (0.6 and 0.2 g [multiply] kg [FFM.sup.-1.] [multiply] 11 [h.sup.-1]; age effect, P [is less than] 0.05). The net protein balance in the supplemented elderly subjects in the fed state was positively correlated with protein intake ([r.sup.2] = 0.46) and in the fasted state was negatively correlated with protein intake ([r.sup.2] = 0.27). The sum of these regressions is a line with increasingly positive net diurnal protein balance produced by increasing protein intake. Conclusion: These data provide evidence of a short-term anabolic response of protein metabolism to dietary supplementation in malnourished elderly patients that is likely to improve muscle strength and functional status. Am J Clin Nutr 2000;71:1129-37. KEY WORDS Elderly subjects, short-term nutritional supplementation, protein-energy malnutrition, body composition, basal metabolic rate, protein turnover, protein accretion, nitrogen isotopes, France

Total parenteral nutrition (TPN) is a method of feeding that supplies all necessary nutrients intravenously; it is used with patients who cannot eat or tolerate a feeding tube. In many cases patients are given TPN because they have become malnourished from the long-term effects of disease. A study was performed to determine whether the addition of insulin to the TPN solution would help malnourished patients gain weight faster and more efficiently. Insulin has an important role in the synthesis of tissues, such as muscle. Sixty patients received TPN with insulin and 75 received TPN without insulin; no subject was diabetic or had glucose intolerance. Body composition was analyzed after two weeks to measure increases in body cell mass (BCM). BCM is the proportion of body tissues made up of functioning, work-performing cells; it is the component that is rapidly depleted during starvation. Both groups, with and without insulin, showed a significant gain in BCM after two weeks of TPN. BCM improvement was greater with higher blood insulin levels, higher caloric intake, and with most severe cases of malnutrition. Older patients showed a slower gain in BCM than younger patients. In conclusion, the addition of insulin to TPN supported a more rapid resolution of malnutrition when compared with standard TPN solutions without insulin. (Consumer Summary produced by Reliance Medical Information, Inc.)