Pancreatitis, Pancreatic Cancer, and Their Metabolic Sequelae: Projected Burden to 2050.

INTRODUCTION: Future burden has been modeled from population-based data for several common gastrointestinal diseases. However, as we enter the third decade in the 21st century, there are no such data on diseases of the pancreas holistically. The study aimed to estimate future incidence of pancreatitis, pancreatic cancer, diabetes of the exocrine pancreas (DEP), and exocrine pancreatic dysfunction (EPD) as well as years of life lost (YLL) due to premature death in individuals with those diseases up to 2050. METHODS: Historical New Zealand nationwide data on hospital discharge, pharmaceutical dispensing, cancer, and mortality were obtained. Annual incidence of each disease and annual YLLs due to premature death in individuals with each disease were calculated. A time series analysis using the stepwise autoregressive method was conducted. RESULTS: Pancreatitis yielded the highest projected incidence (123.7 per 100,000; 95% confidence interval, 116.7-130.7) and YLL (14,709 years; 13,642-15,777) in 2050. The projected incidence and YLL of pancreatic cancer were 18.6 per 100,000 (95% confidence interval, 13.1-24.1) and 14,247 years (11,349-17,144) in 2050, respectively. Compared with pancreatitis and pancreatic cancer, DEP and EPD yielded lower but more steeply increasing projected incidence rates and YLLs. DISCUSSION: The findings suggest that the burden of pancreatitis, pancreatic cancer, DEP, and EPD will rise in the next 3 decades unless healthcare systems introduce effective prevention or early treatment strategies for diseases of the pancreas and their sequelae.

Improved residual fat malabsorption and growth in children with cystic fibrosis treated with a novel oral structured lipid supplement: A randomized controlled trial.

BACKGROUND: In the primary analysis of a 12-month double-blind randomized active placebo-controlled trial, treatment of children with cystic fibrosis (CF) and pancreatic insufficiency (PI) with a readily absorbable structured lipid (Encala™, Envara Health, Wayne, PA) was safe, well-tolerated and improved dietary fat absorption (stool coefficient of fat absorption [CFA]), growth, and plasma fatty acids (FA). OBJECTIVE: To determine if the Encala™ treatment effect varied by severity of baseline fat malabsorption. METHODS: Subjects (n = 66, 10.5±3.0 yrs, 39% female) with baseline CFA who completed a three-month treatment with Encala™ or a calorie and macronutrient-matched placebo were included in this subgroup analysis. Subjects were categorized by median baseline CFA: low CFA (<88%) and high CFA (≥88%). At baseline and 3-month evaluations, CFA (72-hour stool, weighed food record) and height (HAZ), weight (WAZ) and BMI (BMIZ) Z-scores were calculated. Fasting plasma fatty acid (FA) concentrations were also measured. RESULTS: Subjects in the low CFA subgroup had significantly improved CFA (+7.5±7.2%, mean 86.3±6.7, p = 0.002), and reduced stool fat loss (-5.7±7.2 g/24 hours) following three months of EncalaTM treatment. These subjects also had increased plasma linoleic acid (+20%), α-linolenic acid (+56%), and total FA (+20%) (p≤0.005 for all) concentrations and improvements in HAZ (0.06±0.08), WAZ (0.17±0.16), and BMIZ (0.20±0.25) (p≤0.002 for all). CFA and FA were unchanged with placebo in the low CFA group, with some WAZ increases (0.14±0.24, p = 0.02). High CFA subjects (both placebo and Encala™ groups) had improvements in WAZ and some FA. CONCLUSIONS: Subjects with CF, PI and more severe fat malabsorption experienced greater improvements in CFA, FA and growth after three months of Encala™ treatment. Encala™ was safe, well-tolerated and efficacious in patients with CF and PI with residual fat malabsorption and improved dietary energy absorption, weight gain and FA status in this at-risk group.

Lung disease and vitamin D levels in cystic fibrosis infants and preschoolers.

INTRODUCTION: Vitamin D acts on the immune system and lung response. Patients with cystic fibrosis (CF) may be deficient in this vitamin. The aims of the study were to evaluate vitamin D levels and severity of lung disease in infants and preschoolers diagnosed with CF, and to compare them to a group of children without pancreatic insufficiency (PI). METHODS: Patients with CF up to 4 years old were included, and compared to an age-matched group of children without diagnosis of CF. CF group had medical records and High Resolution Thorax Computed Tomography (HRCCT) evaluated in order to verify the severity of lung disease. Information on demographic data, sun exposure habits, supplemental vitamin D therapy, and on the season at the time of vitamin D sampling were collected for both groups. RESULTS: This study included 45 patients in the CF group and 102 in the non-CF group, with no differences in age (P = 0.327) between them. There was no association between vitamin D levels and markers of lung disease in the CF group. The non-CF group had lower daily sun exposure (P = 0.034), and lower supplementation than the CF group (P < 0.001). Supplementation and seasonality were the determinant variables for vitamin D levels, which were lower for non-supplemented children and for assessments during fall/winter. CONCLUSION: There was no association between lung disease severity and vitamin D levels in CF group. Supplementation and seasonality were associated to higher vitamin levels.

Nutritional support and therapy in pancreatic surgery: A position paper of the International Study Group on Pancreatic Surgery (ISGPS).

BACKGROUND: The optimal nutritional therapy in the field of pancreatic surgery is still debated. METHODS: An international panel of recognized pancreatic surgeons and pancreatologists decided that the topic of nutritional support was of importance in pancreatic surgery. Thus, they reviewed the best contemporary literature and worked to develop a position paper to provide evidence supporting the integration of appropriate nutritional support into the overall management of patients undergoing pancreatic resection. Strength of recommendation and quality of evidence were based on the approach of the grading of recommendations assessment, development and evaluation Working Group. RESULTS: The measurement of nutritional status should be part of routine preoperative assessment because malnutrition is a recognized risk factor for surgery-related complications. In addition to patient's weight loss and body mass index, measurement of sarcopenia and sarcopenic obesity should be considered in the preoperative evaluation because they are strong predictors of poor short-term and long-term outcomes. The available data do not show any definitive nutritional advantages for one specific type of gastrointestinal reconstruction technique after pancreatoduodenectomy over the others. Postoperative early resumption of oral intake is safe and should be encouraged within enhanced recovery protocols, but in the case of severe postoperative complications or poor tolerance of oral food after the operation, supplementary artificial nutrition should be started at once. At present, there is not enough evidence to show the benefit of avoiding oral intake in clinically stable patients who are complicated by a clinically irrelevant postoperative pancreatic fistula (a so-called biochemical leak), while special caution should be given to feeding patients with clinically relevant postoperative pancreatic fistula orally. When an artificial nutritional support is needed, enteral nutrition is preferred whenever possible over parenteral nutrition. After the operation, regardless of the type of pancreatic resection or technique of reconstruction, patients should be monitored carefully to assess for the presence of endocrine and exocrine pancreatic insufficiency. Although fecal elastase-1 is the most readily available clinical test for detection of pancreatic exocrine insufficiency, its sensitivity and specificity are low. Pancreatic enzyme replacement therapy should be initiated routinely after pancreatoduodenectomy and in patients with locally advanced disease and continued for at least 6 months after surgery, because untreated pancreatic exocrine insufficiency may result in severe nutritional derangement. CONCLUSION: The importance of this position paper is the consensus reached on the topic. Concentrating on nutritional support and therapy is of utmost value in pancreatic surgery for both short- and long-term outcomes.

Evaluation of energy metabolism and calcium homeostasis in cells affected by Shwachman-Diamond syndrome.

Isomorphic mutation of the SBDS gene causes Shwachman-Diamond syndrome (SDS). SDS is a rare genetic bone marrow failure and cancer predisposition syndrome. SDS cells have ribosome biogenesis and their protein synthesis altered, which are two high-energy consuming cellular processes. The reported changes in reactive oxygen species production, endoplasmic reticulum stress response and reduced mitochondrial functionality suggest an energy production defect in SDS cells. In our work, we have demonstrated that SDS cells display a Complex IV activity impairment, which causes an oxidative phosphorylation metabolism defect, with a consequent decrease in ATP production. These data were confirmed by an increased glycolytic rate, which compensated for the energetic stress. Moreover, the signalling pathways involved in glycolysis activation also appeared more activated; i.e. we reported AMP-activated protein kinase hyper-phosphorylation. Notably, we also observed an increase in a mammalian target of rapamycin phosphorylation and high intracellular calcium concentration levels ([Ca(2+)]i), which probably represent new biochemical equilibrium modulation in SDS cells. Finally, the SDS cell response to leucine (Leu) was investigated, suggesting its possible use as a therapeutic adjuvant to be tested in clinical trials.

A piglet with surgically induced exocrine pancreatic insufficiency as an animal model of newborns to study fat digestion.

The maldigestion and malabsorption of fat in infants fed milk formula results due to the minimal production of pancreatic lipase. Thus, to investigate lipid digestion and absorption and mimic the situation in newborns, a young porcine exocrine pancreatic insufficient (EPI) model was adapted and validated in the present study. A total of thirteen EPI pigs, aged 8 weeks old, were randomised into three groups and fed either a milk-based formula or a milk-based formula supplemented with either bacterial or fungal lipase. Digestion and absorption of fat was directly correlated with the addition of lipases as demonstrated by a 30% increase in the coefficient of fat absorption. In comparison to the control group, a 40 and 25% reduction in total fat content and 26 and 45% reduction in n-3 and n-6 fatty acid (FA) content in the stool was observed for lipases 1 and 2, respectively. Improved fat absorption was reflected in the blood levels of lipid parameters. During the experiment, only a very slight gain in body weight was observed in EPI piglets, which can be explained by the absence of pancreatic protease and amylase in the gastrointestinal tract. This is similar to newborn babies that have reduced physiological function of exocrine pancreas. In conclusion, we postulate that the EPI pig model fed with infant formula mimics the growth and lipid digestion and absorption in human neonates and can be used to elucidate further importance of fat and FA in the development and growth of newborns, as well as for testing novel formula compositions.

Oral cholecalciferol versus ultraviolet radiation B: effect on vitamin D metabolites in patients with chronic pancreatitis and fat malabsorption - a randomized clinical trial.

BACKGROUND: Patients with chronic pancreatitis (CP) often develop fat malabsorption and are susceptible to hypovitaminosis D. AIM: We wanted to evaluate the intestinal uptake of cholecalciferol in patients with CP and fat malabsorption. METHODS: We did a prospective placebo-controlled study including patients with verified CP and fat malabsorption. They were randomized to 10 weeks of (A) ultraviolet radiation B (UVB) 6 min weekly in a commercial tanning bed, (B) vitamin D supplement 1,520 IU/daily, or (C) placebo. The vitamin D metabolites 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (calcitriol) were quantified at the start and end of the study. RESULTS: In total 30 patients were randomized and 27 completed the study. Compliance to tablets and tanning sessions was >80%. The changes in 25OHD levels in group B (32.3 nmol/l; 95% CI 15-50) were significantly greater than changes in group A (p < 0.001) and group C (p < 0.001). Changes in group A (1.1 nmol/l) did not differ from the placebo group (p = 0.9). Changes in calcitriol levels were identical between groups. CONCLUSIONS: Daily vitamin D supplements increased 25OHD in patients with CP compared to placebo whereas weekly tanning bed sessions did not.

Effect of an antioxidant-rich multivitamin supplement in cystic fibrosis.

BACKGROUND: Despite supplementation with standard multivitamins and pancreatic enzymes, deficiencies of vitamins D and K and antioxidants are common in cystic fibrosis (CF). METHODS: In this non-randomized, open-label study, AquADEKs® softgels were given daily over 12 weeks to 14 CF subjects (mean age 15 years, range 10-23) without a preceding wash-out period. Both pancreatic sufficient and insufficient subjects were enrolled. Plasma vitamin and antioxidant levels, urine 8-isoprostane levels, anthropometric measures, and pulmonary function were determined at baseline, 6 and 12 weeks. RESULTS: Daily supplementation significantly increased plasma beta(ß)-carotene, coenzyme Q10, and γ-tocopherol concentrations, decreased proteins induced in vitamin K absence (PIVKA-II) levels, but did not normalize vitamin D and K status in all subjects. Vitamin A levels did not exceed the normal range for any subject during the entire study period. Modest improvements in weight percentile and pulmonary function were observed. Change in plasma ß-carotene concentrations weakly correlated with changes in weight and body mass index percentiles. CONCLUSIONS: In this study, AquADEKs® increased systemic antioxidant levels, while maintaining vitamin A levels in the normal range, and improved but did not completely normalize vitamin D and K status. Increased ß-carotene levels were associated with improved growth parameters. These results warrant further clinical evaluation in CF.

Vitamin D in infants with cystic fibrosis diagnosed by newborn screening.

AIMS: Screening enables early nutritional deficiencies to be detected in those with cystic fibrosis (CF). Although vitamin deficiency is considered unlikely in older subjects with normal vitamin E levels, few studies have determined vitamin D status at diagnosis and its relationship to other fat-soluble vitamins. METHODS: We reviewed vitamin levels in infants diagnosed with CF by newborn screening over a 5-year period in Melbourne, Australia. Vitamin D levels were determined using the IDS gamma-B 25-OH Vitamin D radio-immunoassay (Immunodiagnostic Systems Limited, Boldon, UK). Vitamins A and E were evaluated by high-performance liquid chromatography. We assessed the association between vitamin D level and sex, month of birth, pancreatic status, and vitamin A and E levels. RESULTS: Fifty-eight infants were diagnosed at a median age of 1 month (range: 0-3 months). Initial vitamin D levels were assessed between 0.2 and 3.5 months in 30 (vitamin D) and 45 (vitamins A and E) infants. The number of infants deficient with vitamins D, E and A were 11 (37%), 7 (16%) and 27 (60%), respectively. Vitamin D levels were unrelated to sex, vitamin A or E levels, month of birth or pancreatic status, whereas vitamin A and E levels were significantly lower in those who were pancreatic insufficient. With supplementation, vitamin D increased over time. CONCLUSIONS: Vitamin D deficiency is common in infants newly diagnosed with CF by newborn screening and is unrelated to pancreatic status or predicted low vitamin E levels. Vitamin D deficiency is less common over time following treatment.

Vitamin D insufficiency in children, adolescents, and young adults with cystic fibrosis despite routine oral supplementation.

BACKGROUND: Cystic fibrosis (CF) with pancreatic insufficiency is associated with poor absorption of fat and fat-soluble vitamins, including vitamin D. Pancreatic enzyme supplementation does not completely correct fat malabsorption in CF patients. OBJECTIVE: The objective of the study was to compare the vitamin D status of children, adolescents, and young adults with CF who were treated with routine vitamin D and pancreatic enzyme supplements with the vitamin D status of a healthy reference group from a similar geographic area. DESIGN: Growth, dietary intake, and serum concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and parathyroid hormone (PTH) were measured in 101 white subjects with CF and a reference group of 177 white subjects. RESULTS: The median daily vitamin D supplementation in the CF group was 800 IU. The mean +/- SD serum concentrations of 25(OH)D were 20.7 +/- 6.5 ng/mL in the CF group and 26.2 +/- 8.6 ng/mL in the reference group (P < 0.001). Vitamin D deficiency and insufficiency were defined as 25(OH)D concentrations < 11 ng/mL and < 30 ng/mL, respectively. Seven percent of the CF group and 2% of the healthy reference group were vitamin D deficient (P < 0.03). Ninety percent of the CF group and 74% of the healthy reference group were vitamin D insufficient (P < 0.01). Twenty-five percent of the CF group and 9% of the healthy reference group had elevated PTH (P < 0.006). The odds of vitamin D insufficiency in the CF group, compared with the healthy reference group, were 1.2 (95% CI: 1.1, 1.3) after adjustment for season and age. CONCLUSION: Despite daily vitamin D supplementation, serum 25(OH)D concentrations remain low in children, adolescents, and young adults with CF.

Digestibility rates of major and trace elements in pancreatic duct-ligated pigs.

Ligation of pancreatic duct in pigs leads to a severe maldigestion of calcium and magnesium. Substitution of missing enzymes results in a 'normalization' of the digestibility rates of these elements. In comparison to controls the pre-caecal phosphorus digestibility decreased, but the total digestibility rates increased, after ligation of the pancreatic duct. Furthermore, the total amount of absorbed phosphorus was significantly higher in pancreatic duct ligated pigs. Further studies have to be carried out to investigate, whether phosphorus in exocrine pancreatic insufficiency is excreted with urine, as in this study the observed Ca:P-ratio in blood was in a physiological range. Without a forced renal excretion of phosphorus, consequences and risks (e.g. secondary hyperparathyroidism) of the regulation have to be considered. Regarding the elements sodium, potassium and chloride, an increased faecal excretion could be observed in pancreatic duct ligated pigs. As a substitution with enzyme products led to digestibility rates similar to those in controls, no losses of electrolytes have to be feared. Even though pancreatic juice seems to have influences on the digestibility of investigated trace elements (copper, zinc, iron and manganese), it did not lead to severe imbalances in the corresponding mineral metabolism.

Medium-chain triglyceride absorption in patients with pancreatic insufficiency.

BACKGROUND: The role of medium-chain triglycerides (MCTs) in the management of patients with pancreatic insufficiency is controversial. The aim of the study was to evaluate the absorption of MCTs in the presence of pancreatic insufficiency and the effect of pancreatic extracts on MCT absorption so as to clarify whether the replacement of usual dietary fats with MCTs is cost-effective. METHODS: Six patients with severe pancreatic steatorrhea were for 5 days fed a low-fat diet to which butter (long-chain triglycerides (LCTs)) or MCT oil was added, with and without pancreatic extracts, in a crossover design. RESULTS: Fecal weight and nitrogen losses were the same during MCT and LCT intake. Steatorrhea was substantial during both periods but was significantly lower during MCT than LCT intake. Fecal weight and nitrogen and fat losses were reduced by pancreatic extracts in both diets. Steatorrhea was the same when MCTs and LCTs were consumed together with pancreatic extracts. CONCLUSIONS: MCTs are absorbed better than LCTs in the presence of pancreatic insufficiency but require pancreatic extracts for optimal absorption. No advantage is to be expected from replacing usual dietary fats with MCTs if pancreatic supplements are used.

Oral absorption of omega-3 fatty acids in patients with cystic fibrosis who have pancreatic insufficiency and in healthy control subjects.

Dietary supplementation with fish oils high in the omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, may have an antiinflammatory effect. We determined whether patients with cystic fibrosis (CF) could incorporate omega-3 fatty acids into their plasma and cell membrane phospholipids without adverse effects. In this double-blind study, 12 patients with pancreatic insufficiency who have CF (mean age, 12.2 +/- 5.4 (SD) years) and 13 subjects without CF (mean age, 13.4 +/- 6.3 (SD) years) were randomly assigned to ingest 8 gm daily of either encapsulated fish oil (3.2 gm of eicosapentaenoic acid and 2.2 gm of docosahexaenoic acid daily) or olive oil ethyl esters for 6 weeks. Two of seven and two of five patients with CF who received fish and olive oils, respectively, and one of eight and none of five subjects without CF discontinued taking the capsules before 6 weeks because of eructation or diarrhea. Significant incorporation of omega-3 fatty acids into plasma and erythrocyte membrane phospholipids was observed in subjects with and those without CF randomly assigned to the fish oil treatment. For example, in subjects randomly assigned to receive fish oil, the eicosapentaenoic acid/arachidonic acid ratio in plasma increased 9.8-fold, from 0.04 +/- 0.02 (mean +/- SEM) to 0.39 +/- 0.11 (p = 0.02), in the patients with CF (n = 7) and 23.0-fold, from 0.04 +/- 0.01 to 0.92 +/- 0.17 (p = 0.001), in the subjects without CF (n = 8) who received fish oil (p = 0.02, patients with CF vs subjects without CF at 6 weeks). No clinically or statistically significant changes from baseline were observed in platelet aggregation or levels of vitamin E or A in subjects who received fish oil. Future studies are indicated to determine whether omega-3 fatty acid enrichment provides a clinically beneficial antiinflammatory effect in patients with CF.

Use of famotidine in severe exocrine pancreatic insufficiency with persistent maldigestion on enzymatic replacement therapy. A long-term study in cystic fibrosis.

In patients with pancreatic exocrine insufficiency, the use of pancreatic enzyme does not abolish steatorrhea in some cases. We carried out a long-term prospective study in an attempt to clarify the effectiveness of the associated use of famotidine to enzymatic supplementation on fat absorption and nutritional parameters of patients with pancreatic insufficiency due to cystic fibrosis. We studied 10 patients, mean age 12.5 years, with persistent steatorrhea on enzymatic supplementation. A double-blind crossover design was used and famotidine (1 mg/kg/day) or placebo was given as adjuvant to enzymatic preparations for either of two six-month periods. A statistically significative reduction in fecal wet weight (P less than 0.0001), an improvement in the coefficient of fat absorption (P less than 0.01) and in the steatocrit values (P less than 0.028) were found on famotidine. Moreover, the weight and the height increases were greater after famotidine than after placebo period (respectively, P less than 0.012 and P less than 0.01); also the serum calcium and triglycerides levels were higher after the period on famotidine (respectively, P less than 0.0025 and P less than 0.025). No adverse effects of famotidine were noted. These data suggest that famotidine is a useful adjuvant to pancreatic enzyme therapy in patients with severe pancreatic insufficiency and persistent maldigestion on large doses of pancreatic supplements; in fact, famotidine improves not only fat absorption but the nutritional status of the patients.

Linoleic acid absorption from lipid supplements in patients with cystic fibrosis with pancreatic insufficiency and in control subjects.

To determine the relative role of malabsorption as the cause of decreased linoleic acid in blood and tissue lipids of patients with cystic fibrosis (CF) and pancreatic insufficiency, the increase in plasma linoleic acid was determined after ingestion of various lipid supplements. CF patients with documented pancreatic insufficiency and normal control subjects were given each of four different lipid supplements on separate days (a minimum of 3 days apart). The supplements were commercial safflower oil, Microlipid, Captex 810D, and Captex 810B. Fasting subjects consumed 36 g of lipid in a milk shake containing 15 g of protein and 45 g of carbohydrate. Plasma samples obtained at 0, 2, 4, 6, and 8 h after the meal showed that CF patients absorbed linoleic acid from all of the lipid preparations tested when administered with their regular dose of pancreatic enzyme supplement. The mean maximal increase in percent plasma linoleic acid in CF patients was not different from controls after ingestion of safflower oil, Microlipid, and Captex 810B. With Captex 810D the CF patients had a significantly higher increase in percent plasma linoleic acid than controls, 6.75% vs. 2.27%, respectively, at 2 h (p less than 0.01), and 11.10% vs. 4.65% at 8 h (p less than 0.01). The CF patients also appeared to absorb the Captex products faster than controls, suggesting that presence of medium chain length fatty acids in these structured lipids facilitated their utilization by CF patients. The results indicate that malabsorption alone cannot account for the inadequate or marginal essential fatty acid status of CF patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of pectin and wheat bran on intraluminal pancreatic enzyme activities and on fat absorption as examined with the triolein breath test in patients with pancreatic insufficiency.

In totally pancreatectomized patients breath 14CO2 excretion after ingestion of 14C-labeled triolein was significantly increased by a granulated pancreatic enzyme preparation and was reduced when pectin was added to the enzyme supplement. In the same patients pectin reduced trypsin, lipase, and amylase activities of jejunal aspirates after a test meal supplemented with pancreatic enzyme substitution, which was shown to give good enzyme activities in the intestine. In patients with chronic pancreatitis, breath 14CO2 excretion was reduced by wheat bran, which also caused a reduction in lipase and amylase activities of duodenal aspirates after a test meal. The findings demonstrate the efficiency of treatment with a granulated pancreatic enzyme preparation in restoring intraluminal enzyme activities and fat absorption in patients with pancreatic insufficiency. They also show that pectin and wheat bran may induce fat malabsorption and inhibit digestive enzyme activities in vivo.

[Kinetic tracer studies on protein synthesis during infancy using chemically defined diets containing 15N-lysine as a tracer (author's transl)]. / Tracerkinetische Untersuchungen zur Proteinsynthese im Säuglingsalter mit [alpha 15 N] L-Lysin markierter chemisch definierter Nahrung.

A four-month-old infant with exocrine pancreas insufficiency was fed exclusively on a chemically defined diet. The amino acid formulation of this diet (a supplemented casein hydrolyzate) corresponds to that of breast milk. The 15N labeled lysine tracer (97.4 atom-%) was included in the diet without changing its chemical score. A trace dose of 2.22 mg/kg body weight was applied for 5 days after the infant had been maintained on a chemically defined diet for 11 weeks. Urine was collected over a period of 170 h. The compartment theory was used to calculate the following metabolic data. Cumulative renal 15N excretion showed that nitrogen retention was 90.8%. Protein synthesis amounted to 10.34 g kg-1 d-1 compared with a protein breakdown rate of 8.97 kg-1 d-1. Net protein gain in this infant was about 5.5 g d-1 corresponding to a rate of 1.38 kg-1 d-1 or 13.3% of the synthesis rate. The metabolic pool amounted to 4.96 g N kg-1 d-1. 75.99 mg N kg-1 h-1 was metabolized, mainly to protein, and only about 10% was excreted with the urine.