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Weight gain associated with increased food intake and low habitual activity levels in male adolescent schizophrenic inpatients treated with olanzapine.

OBJECTIVE: The authors studied weight gain mechanisms and energy balance in patients treated with olanzapine. METHOD: The body mass index of male schizophrenic adolescent inpatients treated with olanzapine (N=10) and of 10 matched patients treated with haloperidol (N=10) were measured at baseline and after 4 weeks of treatment. For the patients treated with olanzapine, caloric intake, resting energy expenditure, and physical activity (determined through accelerometry and heart rate monitoring) were assessed at baseline and after 4 weeks of treatment. RESULTS: Body mass index significantly increased in those treated with olanzapine but not in those given haloperidol. The increase in body mass index was due to an increase in caloric intake without change in diet composition. Olanzapine had no significant effect on resting energy expenditure. Daily energy expenditure was very low before and after treatment. CONCLUSIONS: Olanzapine-induced weight gain is associated with a general increase in caloric intake.

Adolescent↗

Effects of diets with different content in protein and fiber on embryotoxicity induced by experimental diabetes in rats.

Three groups of streptozotocin-diabetic rats were maintained during pregnancy on three hyperproteic diets with different protein contents. These differences were compensated by an equal quantity of fiber (group 1: protein 55.0%, fiber 4.5%; group 2: 45.0%, 14.0%; group 3: 35.0%, 24.0%). Three groups of nondiabetic pregnant rats were fed with the same diets and served as control. The differences of the daily protein intake among the diabetic groups were less pronounced than those expected on the basis of the diet composition, and the embryopathic effects (reduced fetal weight, increased in malformation and resorption rate) were not statistically different among the three groups of diabetic animals. The frequency of congenital malformations was higher than that observed in a previous experiment in diabetic rats maintained on a standard diet, but much lower than that observed in animals fed on a purified, fiber-poor, normoproteic diet. When the caloric intake of the diabetic rats in the different groups was determined it was found to be similar for all of them and also similar to the caloric intake of the rats given a standard nonteratogenic diet (in previous experiments), while the rats maintained on a normoproteic, teratogenic diet increased their caloric intake. These results seem to indicate that the diet composition greatly influences the intake of food and calories of pregnant diabetic rats and this may play a role in modulating the embryopathic effect of diabetes.

Analysis of Variance↗

[Nutritional status of patients with type 1 and 2 diabetes in Belgium].

The aim of this study was to evaluate the daily caloric intake as well as the distribution of carbohydrates, fat, protein and alcohol in a Belgian population with type 1 and 2 diabetes, in the view of the recent ADA recommendations. Dietary intake and repartition of nutriments was based upon the three days evaluation recall. Our results show excessive caloric intake in type 2 diabetic patients when compared with type 1 subjects (2652 +/- 850 vs. 2271 +/- 546 Kcal/day; P < 0.005). We also show an inadequate repartition of carbohydrates (41 +/- 5 and 39 +/- 6% in type 1 and 2 diabetic patients, respectively) and lipids (39 +/- 5 and 39 +/- 7%). Protein intake was 16% of the total caloric amount. Fibers intake was adequate. High consumption of alcohol was assessed in both type 1 and 2 diabetic patients. In conclusion, our data evidenced several pitfalls in the diet of type 1 and 2 diabetic patients. They emphasize the need for more (and repeated) practical diabetic information in order to improve daily nutritional habits.

Adult↗

How does a suicide attempter eat differently from others? Comparison of macronutrient intakes.

OBJECTIVE: Issues of the subtle effects of diet and nutrition on suicidal behaviors are rarely examined. This study describes the differences in dietary intakes of macronutrients between individuals who had ever made a suicide attempt and those who never had. METHODS: We examined the data of 7631 non-institutionalized adults ages 17 to 39 y who completed a mental disorder diagnostic interview and a 24-h dietary recall as a part of the Third National Health and Nutrition Examination Survey, 1988 to 1994. Multivariable adjusted means of daily caloric intake and energy percentage from macronutrients were calculated for individuals who had a history of lifetime suicide attempt(s) (n = 408) and compared with those who did not. RESULTS: After adjustment for covariates, including socioeconomic indicators, health risk factors, and history of medical and psychiatric illnesses, we observed that the means of daily caloric intake, cholesterol, and energy percentages from carbohydrate, total fat, saturated fat, monounsaturated fat, and protein did not differ significantly between attempters and non-attempters. However, energy percentage from polyunsaturated fat was lower in attempters than in non-attempters. Mean percentages +/- standard error for smoking attempters, non-smoking attempters, smoking non-attempters, and non-smoking non-attempters were 5.5 +/- 0.4 (P = 0.01), 6.7 +/- 0.2 (P = 0.02), 7.5 +/- 1.4 (P = 0.78), and 7.2 +/- 0.1 (reference), respectively, in men, and 6.3 +/- 0.4 (P = 0.01), 7.2 +/- 0.2 (P = 0.07), 7.3 +/- 1.0 (P = 0.89), and 7.5 +/- 0.1 (reference), respectively, in women. Dietary fiber intake was also lower in attempters than in non-attempters. These differences were independent of daily caloric intake. CONCLUSIONS: Individuals with a history of suicide attempt have low intakes of polyunsaturated fat and fiber. Potential deleterious effects of low intake of polyunsaturated fat and fiber among suicide attempters merit further investigation.

Adolescent↗

Somatomedin and growth hormone in psychosocial dwarfism.

The diagnosis of psychosocial dwarfism (PSD) was made in a 7 year old boy upon admission to the hospital. In the period following admission, he grew at a slightly accelerated rate of 0.6 cm in 24 days (extrapolated growth rate--9.1 cm/yr); his caloric intake was 1663 calories/day (147 cal/kg/day), stimulable growth hormone was 5.9 ng/ml and somatomedin activity was in the hypopituitary range (0.24, 0.05 U/ml). In the following period of marked catch-up growth of 8.6 cm in 102 days (extrapolated growth rate 30.8 cm/yr), his caloric intake decreased significantly to 1514 cal/day (106 cal/kg/day, 0.005 less than p less than 0.01), stimulable growth hormone in this period was 13.6 ng/ml and somatomedin activity normalized (0.98 U/ml). While under continued observation, with separation from his favorite nurse, his growth velocity dropped significantly to the rate immediately following admission, but there was no change in his stimulable growth hormone or in somatomedin activity. With the return of his favorite nurse, he resumed his previous rapid catch-up growth with no change in caloric intake (p equals not significant), growth hormone level, or somatomedin activity. Upon transient return to his depriving home, his growth rate decreased to 1.4 cm in 70 days (extrapolated growth rate 7.2 cm/yr); growth hormone remained in the normal range. Somatomedin activity was in the low normal range (0.57 U/ml) and rose to high normal activity (1.31 U/ml) as rapid catch-up growth resumed after he had been readmitted. We conclude from these data that: 1. Serum somatomedin in longstanding untreated PSD may be in the hypopituitary range. 2. Markedly fluctuating growth rates during recovery in this patient with PSD were not due to changes in caloric nutrition, growth hormone release or somatomedin activity, but to an as yet unidentified factor affecting growth during emotional stress.

Affective Symptoms↗

Calories, fat and cancer.

The experiments reported are part of our effort to dissociate the tumor-enhancing effects of dietary fat and high caloric intake. Rats either were fed ad libitum diets containing 4% corn oil or their calories were restricted by 40% and their diets contained 13.1% corn oil. Incidence of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors was 80% in rats fed ad libitum and 20% in those fed the calorie-restricted diets. Incidence of 1,2-dimethylhydrazine (DMH)-induced colon tumors was 100% in rats fed ad libitum and 53% in those whose caloric intake was restricted by 40%. The tumor yield (tumors per tumor-bearing rat) was significantly lower in rats on caloric restriction. In another series, rats were fed diets containing 5, 15 or 20% corn oil ad libitum or were fed calorie-restricted (by 25%) diets which provided 20 or 26.6% corn oil (therefore, the same absolute amount of fat was consumed in each of the pair-fed groups). Tumor incidence and tumor yield in the two calorie-restricted groups were similar to those seen in the rats fed 5% fat ad libitum; tumor burden (total g of tumor) was 45-65% lower in the calorie-restricted rats. The data suggest that caloric intake is a more stringent determinant of tumor growth than fat intake.

9,10-Dimethyl-1,2-benzanthracene↗

Glucagon-like peptide 1 as a regulator of food intake and body weight: therapeutic perspectives.

After ingestion of carbohydrate- and fat-rich meals, the incretin hormone glucagon-like peptide 1 (GLP-1) is secreted from the L-cells in the distal put into the circulation. Its major physiological effect lies in a strongly glucose-dependent stimulation of insulin secretion from pancreatic B-cells. Furthermore, GLP-1 suppresses glucagon secretion, stimulates B-cell neogenesis as well as proinsulin biosynthesis and inhibits gastric emptying and acid secretion. Recently, GLP-1 could be shown to reduce caloric intake and to enhance satiety, most likely via specific receptors within the central nervous system, resulting in reduced weight gain in experimental animals. In nondiabetic and Type 2 diabetic human subjects, exogenous GLP-1 reduces hunger, caloric intake and body weight. Therefore, in addition to its well-characterized antidiabetogenic effect, the anorectic effect may offer GLP-1 a potential in the pharmacotherapy of obesity. It is still unknown whether the GLP-1 effect on caloric intake is sustained after long-term treatment. Furthermore, the exact mechanisms by which the peptide exerts its biological effects have not yet been clarified. Due to the rapid degradation of native GLP-1, its therapeutic application is limited by the short half-life. Therefore, suitable modes of administration are needed in order to reach stable plasma concentrations. The present review aims to describe the role of GLP-1 in the central regulation of feeding and to discuss its possible application in the pharmacotherapy of obesity.

Animals↗

Prevalence, outcome and associated factors of deranged liver function tests in patients on home parenteral nutrition.

INTRODUCTION: The prevalence of deranged liver function tests (LFT) in patients on long-term home parenteral nutrition (HPN) is poorly documented. The aim of our study was to document the prevalence of this complication and possible associated factors. METHOD: Retrospective analysis of case notes of 107 patients on HPN was performed. Deranged LFT was defined as any biochemical parameter of LFT that is 1.5 times above the reference range. RESULTS: There were 39 males and the median age was 51 (range 20-73) years old. Median duration of HPN was 40 (range 6-252) months. Underlying diagnoses were Crohn's disease (40%), ischaemic bowel disease in 28.1% (arterial or venous), post-surgical intestinal adhesion and fistula (16.9%) and others (21.7%). The mean energy intake from HPN was 1003+/-544(SD) kcal/day with 845+/-474 kcal/day from glucose, 157+/-127 kcal/day from fat and mean nitrogen intake was 6.2+/-3.6 g/day. Raised alkaline phosphatase (mean 197+/-143(SD)U/L) was the most common abnormality (40 patients). Two patients had hyperbilirubinaemia; one patient had hereditary spherocytosis and in the other patient, the cause could be attributed to HPN with bilirubin of 54 micromol/l. Fifty-one patients (47.7%) had deranged LFT as judged from raised parameters on LFT. Abnormality in LFT was transient in nine patients. For the other 42 patients (39%), abnormalities in LFT remained stable for median duration of follow-up of 18.5 (range 3-180) months. No patients developed decompensated liver disease. On univariate analysis, length of small bowel of less than 100 cm, a higher total caloric intake from HPN (mean 1117+/-486 kcal against 907+/-576 kcal, P<0.05), and higher daily caloric intake from HPN in relation to calculated daily energy requirement (70+/-32% against 57+/-36%) were noted to be significantly associated with deranged LFT. However, on multivariate analysis, length of small bowel of less than 100 cm was the only significant variable for deranged LFT. CONCLUSION: Our finding showed the prevalence of deranged LFT to be 39% and raised alkaline phosphatase was the most common abnormality. Length of small bowel of less than 100 cm was found to be a significant independent variable for deranged LFT and the reason for this observation could be due to higher parenteral caloric intake. In our experience, LFT abnormalities are associated with a good prognosis as none of the patients developed decompensated liver disease.

Adult↗

Energy expenditure, substrate oxidation, and body composition in subjects with chronic alcoholism: new findings from metabolic assessment.

There is some controversy as to the effect of ethanol on body weight and alcohol energy contribution to body mass. The aim of this study was to evaluate the effect of alcohol addiction on resting energy expenditure (REE) and body composition. Twelve patients with current alcoholism (A) without severe liver disease or lipid and carbohydrate malabsorption were compared with a group of healthy social drinkers (B) matched for sex, age, and height. Their caloric intake was computed on the basis of a food diary. REE was measured with indirect calorimetry, and body composition was assessed by both anthropometry and bioimpedance. A significant decrease in fat mass in A compared with B was found (14.8 +/- 5.39 vs. 19.0 +/- 3.50 kg; p < 0.05). No significant differences were observed in fat-free mass (FFM) or in total body water between the two groups. A showed higher REE values normalized by FFM than B (35.5 +/- 2.97 vs. 33.0 +/- 2.95 kcal/kgFFM; p < 0.05). The nonprotein respiratory quotient was significantly lower in A than in B (0.76 +/- 0.03 vs. 0.86 +/- 0.03; p < 0.001), and A showed significantly higher lipid oxidation and lower carbohydrate oxidation than B (p < 0.05). The daily caloric intake provided only by food ingestion was found to be significantly higher in controls, but because the percentage of alcohol calories of total energy intake was 46.3 +/- 6.80 in alcoholics and 13.6 +/- 3.59 in controls (p < 0.0001), the total caloric intake, computed as food intake plus alcohol intake, was higher in alcoholics than in control subjects. No statistical differences were found in urinary nitrogen excretion and fecal loss between groups. Patients with alcoholism showed an increased REE over predicted values and a preferential lipid oxidation with respect to controls; these findings could be related to induction of microsomal ethanol oxidizing system and to mitochondrial function adaptation secondary to chronic alcohol abuse. In either case, the effects of such changes in energy metabolism may contribute to alcohol associated hepatic injury.

Adult↗

Use of pup in a cup model to study gastrointestinal development: interaction of nutrition and pituitary hormones.

The novel technique of artificial rearing (AR) of rat pups circumvents the difficulty of controlling diet composition and caloric intake. For studies of effects of nutrition and hormone interactions on gastrointestinal development, an appropriate experimental approach is to use AR rats whose corticosterone production is inhibited or abolished. Hypophysectomized (Hx) rats were used to examine whether growth retardation after Hx results from reduced caloric intake. Hx, sham-Hx and intact rats were isocalorically fed a cow-milk formula from day 12 to 18. Mother-fed (MF) Hx and intact rats were used as baseline controls. MF-Hx showed retarded intestinal growth, decreased body weight gain and reduced skeletal growth. In contrast, AR-Hx rats showed intestinal hypertrophy, normal body weight gain and reduced skeletal growth. Intestinal lactase activity remained higher in MF-Hx or AR-Hx rats than in control groups. AR-Hx rats showed no precocious increase of intestinal maltase and sucrase activity as did AR controls. Trace levels of serum growth hormone was detectable in MF-Hx but not in AR-Hx rats. We conclude that caloric intake can promote intestinal and somatic growth in the absence of the pituitary gland and pituitary hormones are required for skeletal growth and intestinal enzymic differentiation.

Animals↗

Effects of the lipase inhibitor orlistat on intake and preference for dietary fat in rats.

Orlistat (Ols), a potent inhibitor of pancreatic lipase, was added to the fat source (1 or 4 mg Ols/g fat) of a macronutrient self-selection diet fed to adult female rats. The rats responded to the drug-induced reduction in fat absorption by decreasing their dietary fat intake and increasing their protein and carbohydrate intake in a dose-related manner. Total caloric intake also increased, but body weight gain was inhibited compared with the nondrug control group. When Ols was removed from the diet, nutrient selection, caloric intake, and body weight returned to control levels. In additional short-term experiments (30 min/day), rats developed a preference for a plain fat diet over an Ols-fat diet (4 mg/g fat) and also for a cue flavor paired with plain fat over a flavor paired with Ols-fat. Yet, when not given the choice, the rats consumed nearly as much Ols-fat as plain fat diet. These results indicate that, by reducing fat absorption, Ols reduced the attractiveness of dietary fat, although it did not make the fat diet aversive. In clinical use, lipase inhibitors may be effective in reducing dietary fat intake by reducing both the consumption and absorption of fat.

Animals↗

[Evaluation of the effect of a "Mediterranean diet" and pre-pregnancy body mass on fetal growth].

In this study we compared the pregravidic body mass index (Quetelet index) with some variables recorded during pregnancy (caloric intake; weight increase, neonatal birth weight) in a group of patients consumers of a typical mediterranean diet. We studied the dietary habits of 100 pregnant women with gestational ages between 13 and 38 weeks. Each woman has been provided with daily, for seven consecutive days. The data have been analyzed evaluating, for each dietary componene, the caloric, proteic, glucidic, lipidic and microelements share. Our results showed degree of pregravidic obesity. However also in overweight patients that used diets with caloric intake as low as about 1600 Kcal/day, the neonatal weights were always within the normal range, confirming the adequacy of the "mediterranean diet" to the specific nutritional needs in pregnancy. Neonatal weight was better correlated to the pregravidic IQ than to the caloric intake.

Adult↗

Human plasma ghrelin levels increase during a one-year exercise program.

Weight loss resulting from decreased caloric intake raises levels of the orexigenic hormone, ghrelin. Because ingested nutrients suppress ghrelin, increased ghrelin levels in hypophagic weight loss may result from decreased inhibitory input by ingested food, rather than from lost weight. We assessed whether ghrelin levels increase in response to exercise-induced weight loss without decreased caloric intake. We randomized 173 sedentary, overweight, postmenopausal women to an aerobic exercise intervention or stretching control group. At baseline, 3 months, and 12 months, we measured body weight and composition, food intake, cardiopulmonary fitness (maximal oxygen consumption), leptin, insulin, and ghrelin. Complete data were available for 168 women (97%) at 12 months. Exercisers lost 1.4 +/- 0.4 kg (P < 0.05 compared with baseline; P = 0.01 compared with stretchers) and manifested a significant, progressive increase in ghrelin levels, whereas neither measure changed among stretchers. Ghrelin increased 18% in exercisers who lost more than 3 kg (P < 0.001). There was no change in caloric intake in either group and no effect on ghrelin of exercise per se independent of its impact on body weight. In summary, ghrelin levels increase with weight loss achieved without reduced food intake, consistent with a role for ghrelin in the adaptive response constraining weight loss and, thus, in long-term body weight regulation.

Body Mass Index↗

Dietary energy and fat content as factors in the nutrition of developing egg strain pullets and young hens. 4. Effect on growth, hepatic lipogenic enzyme activity and body chemical composition of White Leghorn pullets from hatch to 20 weeks of age.

Nine starting and rearing diets (three energy levels each with three fat levels) were fed to commercial White Leghorn chicks from hatch to 20 weeks of age. As noted in the earlier papers of this series, pullets fed the high energy rearing diets showed significant (P = 0.05) reductions in feed intake, however, average daily caloric intake was greater (P = 0.05) for pullets consuming the low energy rearing diets. Fat content of the diet had not influence on either daily feed (g.) or caloric (kcal.) intake. Energy content of the diets failed (P = 0.05) to affect parameters related to body growth and development, hepatic citrate-cleavage and "malic" enzyme activity and liver or body composition. Fat content of the diet depressed hepatic enzyme activity while no effect was noted on body weight, liver weight or body composition. The onset of sexual maturity altered lipid metabolism in the developing pullets. Significant (P = 0.05) energy level by fat level interactions were noted in only two of the 20 parameters studied in this experiment. In vitro assay of hepatic citrate-cleavage and "malic" enzyme activity proved to be of little value in predicting hepatic lipogenic activity and subsequent effects on liver and total body composition.

ATP Citrate (pro-S)-Lyase↗

Increased susceptibility to diet-induced obesity in histamine-deficient mice.

BACKGROUND AND AIM: The neurotransmitter histamine is involved in the regulation of appetite and in the development of age-related obesity in mice. Furthermore, histamine is a mediator of the anorexigenic action of leptin. The aim of the present study was to investigate a possible role of histamine in the development of high-fat diet (HFD)-induced obesity. METHODS: Histamine-deficient histidine decarboxylase knock-out (HDC-KO) mice and C57BL/6J wild-type (WT) mice were given either a standard diet (STD) or HFD for 8 weeks. Body weight, 24-hour caloric intake, epididymal adipose tissue size, plasma leptin concentration and quantitative expression of leptin receptor (Ob-R) mRNA were measured. RESULTS: Both HDC-KO and WT mice fed an HFD for 8 weeks increased their body weight significantly more than STD-fed mice. A significant difference in body weight gain between HDC-KO mice fed an HFD or an STD was seen after 2 weeks, whereas a significant difference in body weight gain was first observed after 5 weeks in WT mice. After 8 weeks 24-hour caloric intake was significantly lower in HFD- than in STD-fed WT mice. In HDC-KO mice no difference in caloric intake was observed between HFD- and STD-fed mice. After 8 weeks epididymal adipose tissue size and plasma leptin concentration had increased significantly in HFD-fed WT and HDC-KO mice compared to their STD-fed controls. Epididymal adipose tissue size was higher in HDC-KO than WT mice, both in STD- and HFD-fed mice. A significant decrease in Ob-R mRNA in HFD-fed HDC-KO mice compared to STD-fed HDC-KO mice was observed, while no such difference was observed in WT mice. CONCLUSION: Based on our results, we conclude that histamine plays a role in the development of HFD-induced obesity.

Adipose Tissue↗

Introduction of a high-energy diet acutely up-regulates hypothalamic cocaine and amphetamine-regulated transcript, Mc4R and brown adipose tissue uncoupling protein-1 gene expression in male Sprague-Dawley rats.

Obesity is an escalating problem in Western societies. Susceptibility to weight gain within an obesogenic environment is variable. It remains unclear how the range of weight gain responses are generated. It is possible that an individual's immediate and/or sustained appetite for apparently palatable foods, or metabolic adaptations to a new diet could be important. The present study therefore examined the short- to medium-term effects of a high-energy (HE) diet on bodyweight, food intake, and energy balance-related signalling systems. Sprague-Dawley rats were fed either chow or an HE diet for 12 h, 24 h, 48 h or 14 days. Blood hormones and metabolites were assayed, and expression of uncoupling protein-1 (UCP-1) and hypothalamic energy-balance related genes were determined by Northern blotting or in situ hybridisation, respectively. Short-term exposure (12 h, 24 h, 48 h) to the HE diet had no effect on grams of food consumed, but caloric intake was increased. Exposure to HE diet for 14 days (medium term) established a bodyweight differential of 7.7 g, and animals exhibited a transient increase in caloric intake of 5 days duration. Terminal levels of leptin, insulin, glucose and non-esterified fatty acids (NEFAs) were all increased in HE-fed animals. UCP-1 mRNA was elevated in interscapular brown adipose tissue from HE-fed rats only at 12 h. Cocaine and amphetamine-regulated transcript (CART) and Mc4R gene expression in the hypothalamus were increased after 12 h and 24 h on an HE diet, respectively. The rats appear to passively over-consume calories as a result of consuming a similar weight of a more energy dense food. This evokes physiological responses, which adjust caloric intake over several days. Circulating NEFA and insulin concentrations, UCP-1, Mc4R and CART gene expression are increased as an immediate consequence of consuming HE diet, and may be involved in countering hypercaloric intake. Circulating leptin is increased in the HE-fed animals after 48 h, reflecting their increasing adiposity.

Animal Feed↗

The determinants of protein catabolism in neonates on extracorporeal membrane oxygenation.

BACKGROUND/PURPOSE: Protein catabolism appears to be markedly elevated among neonates on extracorporeal membrane oxygenation (ECMO). The aim of this study was to determine the effect of dietary caloric intake on protein catabolism in neonates on ECMO to help construct therapies that may promote anabolism. METHODS: Twelve total parenteral nutrition (TPN)-fed (88.1 +/- 5.0 [SE] kcal/kg/d; range, 60 to 113 kcal/kg/d; 2.3 +/- 0.2 g/kg/d protein) neonates were studied on ECMO at day of life 7.2 +/- 0.8 d. Protein kinetics were determined using infusions of NaH13CO3 and 1-[13C]leucine. RESULTS: As expected, C-reactive protein levels were significantly elevated compared with normal controls (44.0 +/- 7.6 mg/L v 1.9 +/- 1.1 mg/L; P < .001). Negative protein balance (-2.3 +/- 0.6 g/kg/d; range, 1 to -6.4 g/kg/d) highly correlated (r = -0.88, P < .001) with total protein turnover. Increased dietary caloric intake correlated with increased amino acid oxidation (r = 0.85, P < .001), increased total protein turnover (r = 0.73, P < .01), continued negative protein balance (r = 0.72, P < .01), increased whole-body protein breakdown (r = 0.66, P < .05), and increased CO2 production rate (r = 0.73, P < .01). CONCLUSIONS: A surplus of dietary caloric intake does not improve protein catabolism and merely increases CO2 production in these highly stressed neonates. Thus, judicious caloric supplementation is warranted.

C-Reactive Protein↗

Ventilatory drive in normal man during semistarvation.

The effects of reduced caloric intake on ventilatory drive were investigated in normal volunteers. During a ten-day semistarvation period, six subjects (group 1) received parenterally an amino acid solution providing 550 kcal/d sufficient to prevent a negative nitrogen balance. Six subjects (group 2) received in addition a safflower oil solution providing a total caloric intake of 1,100 kcal/d. Hypoxic ventilatory drive was estimated by an index (parameter A) of the relation between minute ventilation (VE) and hypoxia. In group 1, mean values (+/- SEM) of A decreased significantly from 161.5 (+/- 42.0) to 48.9 (+/- 12.0) by day 10 (p less than 0.05), indicating a severe depression of hypoxic drive despite a positive nitrogen balance. In group 2, A did not change significantly (p greater than 0.05) from control values indicating a preserved hypoxic ventilatory drive. In both groups, the slopes of the line relating VE to arterial PCO2 (delta VE/delta PaCO2) did not change significantly during the ten-day semistarvation period consistent with preservation of the hypercapnic ventilatory drive. These data indicate that during periods of starvation, parenteral administration of aminoacids in an amount sufficient to maintain nitrogen balance is inadequate to prevent depression of respiratory control mechanisms unless a minimum daily caloric intake is achieved.

Adult↗