Body surface area-based omega-3 fatty acids supplementation strongly correlates to blood concentrations in children.

Omega-3 fatty acids have been suggested as a complement in cancer treatment, but doses are not established. We performed a dose-finding study in 33 children in remission from cancer. Participants were allocated to a body surface area (BSA) adjusted dose (mg/m2) of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (40:60), ranging 233-3448 mg/m2 daily for 90 days. Fatty acid concentration in plasma phospholipids and red blood cells were determined by GC. Supplementation was well tolerated and correlated strongly with blood ω3-fatty acid concentrations and EPA showed the highest increase. Using the ω3-index disregards docosapentaenoic acid (DPA), which increased 30-43% in our study motivating an EDD-index (∑EPA,DPA,DHA). The ratio between arachidonic acid and EPA or DHA showed negative exponential trends. Dose per BSA enabled an individualized omega-3 supplementation decreasing the variation referred to interindividual differences. Based on our results, we suggest a dose of 1500 mg/m2 BSA for further studies.

Polyamine levels in breast milk are associated with mothers' dietary intake and are higher in preterm than full-term human milk and formulas.

BACKGROUND: Polyamine intake from milk is considered essential for post-natal maturation of the immune system and small intestine. The present study aimed to determine polyamine content in human milk after preterm delivery and the association with mothers' dietary intake. In comparison, the polyamine levels were compared with those in term breast milk and some corresponding formulas. METHODS: Transitional breast milk was collected from 40 mothers delivering after 24-36 weeks of gestation, and from 12 mothers delivering after full term. Food intake was assessed in mothers delivering preterm babies using a 3-day diary. Polyamines were analysed by high-performance liquid chromatography. RESULTS: The dietary intake of polyamines was significantly associated with breast milk content but weaker for spermine than for spermidine and putrescine. Total polyamine level was higher in preterm than term milk and lower in the corresponding formulas. Putrescine, spermidine and spermine contents [mean (SEM)] in preterm milk were 165.6 (25), 615.5 (80) and 167.7 (16) nmol dL⁻¹, respectively, with the levels of putrescine and spermidine being 50% and 25% higher than in term milk. The content of spermine did not differ. CONCLUSIONS: Dietary intake of polyamines has an impact on the content in breast milk. The difference between human milk after preterm and term delivery might be considered when using donor human milk for preterm infants. The corresponding formulas had lower contents. Further studies are important for determining the relationship between tissue growth and maturation and optimal intake.

Nervonic acid is much lower in donor milk than in milk from mothers delivering premature infants--of neglected importance?

Nervonic acid is important for white matter development and its incorporation increases rapidly in the last trimester, but few studies focus on this fatty acid. Other mother's milk, usually after term delivery, is often used for premature infants, whose mothers cannot breastfeed. The fatty acid (FA) concentrations were analyzed by gas chromatography in 12 samples of donor human milk (DHM) from five mothers, and compared to milk from 42 mothers delivering preterm infants. Fat, lactose and protein contents were compared. Nervonic acid showed sevenfold higher concentrations and LCPUFA 90% higher concentrations in premature milk compared to DHM. Linoleic acid was found in 43% higher concentrations in DHM than in premature milk. The fat and protein contents were lower in DHM. Our results suggest that studies are warranted to investigate if DHM given to premature infants may require supplementation of nervonic acid, and not only LCPUFA, protein and minerals.

Lower polyamine levels in breast milk of obese mothers compared to mothers with normal body weight.

BACKGROUND: Obesity is associated with risks for mother and infant, and the mothers' dietary habits influence breast milk composition. Polyamines are secreted in breast milk and are essential for the regulation of intestinal and immune function in newborns and infants. The present study aimed to investigate the level of polyamines in human milk obtained from obese and normal weight mothers at different times of lactation. METHODS: Breast milk from 50 mothers was obtained at day 3, and at 1 and 2 months after delivery. The mothers had normal body weight [body mass index (BMI) < 25 kg m(-2) ] or were obese (BMI > 30 kg/m(2) ). A subgroup of obese mothers participated in a weight reduction programme during pregnancy. Polyamines were analysed using high-performance liquid chromatography. RESULTS: The total polyamine content was significantly lower at all times in breast milk from obese mothers compared to milk from controls. Spermine levels did not differ between groups at any time in contrast to the levels of putrescine and spermidine. Putrescine concentrations were highest on day 3 and spermidine and spermine were highest at 1 month of lactation. The obese mothers, who received dietary advice during pregnancy based on the Nordic Nutrition Recommendations, had higher concentrations of putrescine and spermidine in their milk than the obese mothers without any intervention. CONCLUSIONS: Polyamine concentrations were lower in breast milk from obese mothers compared to mothers with a normal weight. General dietary intervention in obese mothers increased the polyamine levels, suggesting that the low levels in obesity were at least partly associated with food habits. However, the consistency of spermine suggests a special metabolic function of this polyamine.

Different fatty acid pattern in breast milk of obese compared to normal-weight mothers.

INTRODUCTION: The aim of this study was to investigate the fatty acid (FA) pattern in breast milk of obese mothers and their neonates' plasma compared to those of normal weight mothers. PATIENTS AND METHODS: This was an observational study of 41 obese and 41 normal weight pregnant women. Twenty-nine obese women participating in a weight reduction program were investigated for comparison. FAs were analyzed in breast milk collected at 3 and 10 days and one and two months postnatally and in infant's plasma 3 days after birth. RESULTS AND CONCLUSIONS: The concentration of long-chain n-3 FA were lower and the ratio n-6/n-3 FA higher in neonates and in consecutive samples of breast milk of obese mothers compared to normal weight mothers. The obese mothers that participated in an intervention program with general dietary advice had FA concentrations approaching that of the normal-weight mothers. The study indicates importance of dietary advice in pregnancy.

Motor, mental and behavioral developments in infancy are associated with fatty acid pattern in breast milk and plasma of premature infants.

The objective of this study was to investigate any association between infants' early development and PUFA concentrations in early breast milk and infants' plasma phospholipids at 44 weeks gestational age. Fifty-one premature infants were included. The quality of general movement was assessed at 3 months, and motor, mental and behavioral development at 3, 6, 10 and 18 months corrected age using Bayley's Scales of Infant Development (BSID-II). Linoleic acid, the major n-6/n-3 FA ratios, Mead acid and the EFA deficiency index in early breast milk were negatively associated with development up to 18 months of age. DHA and AA, respectively, in infants' plasma phospholipids was positively, but the AA/DHA ratio negatively, associated with development from 6 to 18 months of age. Our data suggest that the commonly found high n-6 concentration in breast milk is associated with less favorable motor, mental and behavioral development up to 18 months of age.

Fatty acid composition of diet, cord blood and breast milk in Chinese mothers with different dietary habits.

The influence of two different dietary patterns on maternal fatty acid (FA) intake on the composition of umbilical cord blood plasma phospholipids and transitional breast milk was investigated. A 7-day dietary record was completed in the last trimester of pregnancy by women living in an inland and a coastal area of south-eastern China. The FA composition in maternal diet was calculated using the 2002 Chinese food composition database. Cord blood and transitional breast milk samples were collected and their FA composition was analyzed by capillary gas-liquid chromatography. Mothers in the coastal area showed higher intake of long-chain polyunsaturated FA (LCPUFA) including docosahexaenoic acid (DHA, 22:6omega) and eicosapentaenoic acid (EPA,20:5omega3) but lower linoleic acid (LA, 18:2omega6) and alpha-linolenic acid (ALA, 18:3omega3) than the mothers in the inland area. The intake of arachidonic acid (AA, 20:4omega6) did not differ between the two areas. LA, ALA, AA and DHA in breast milk of day 5 reflected the maternal diet except that the EPA content in breast milk at day 5 was similar for the areas. LA, ALA and AA were lower and EPA higher in umbilical cord plasma phospholipids in infants from the costal compared to the inland area. There were significant differences in maternal intakes of FA confirming different dietary habits, which influenced the FA composition of cord plasma phospholipids and transitional breast milk. Since FA influence gene expression the found variation implies that the long-term follow-up of this cohort will be interesting.

Muscular strength after different types of training in physically active patients with cystic fibrosis.

Physical training is important in the treatment of patients with cystic fibrosis (CF). Optimal types of training and intensity are unknown. The aim of the study was to evaluate the effect on muscular strength after 6 months of endurance training (ET) and/or resistance training (RT). Twenty patients (eight females) participated, 16-35 years, with mean forced expiratory volume in 1 s 91% of the predicted. ET or RT for 30-45 min three times a week for 3 months was followed by a mixed program for another 3 months. Heart rate recording, diaries and frequent personal contacts were used for monitoring. Vitamin E and cytokines were analyzed. Fifteen tests of muscular strength were used. Handgrip strength in females and quadriceps strength in males were significantly decreased compared with healthy age- and sex-matched controls and positively associated with lung function. Sixteen patients completed the program. By ET, quadriceps strength was further decreased and after 6 months quadriceps isometric strength was also decreased in females. There was a tendency toward different effects on the serum levels of IL-6 and vitamin E by the different types of training. CF patients showed no improvements in muscular strength after 6 months of controlled training, suggesting a physiological muscular impairment despite normal anthropometry, but associated with lung function.

Fatty acid composition in breast milk and serum phospholipids of healthy term Chinese infants during first 6 weeks of life.

AIM: To compare the fatty acid (FA) pattern in early and mature breast milk with that in plasma phospholipids of cord blood and breast-fed infants. METHODS: Forty-five mother-infant pairs from western Shanghai were studied. All infants, born at term with normal weight and length, were examined at birth and days 5 and 42. FA was analyzed by capillary gas-liquid chromatography. RESULTS: Cord blood showed higher concentration of long-chain polyunsaturated FA (LCPUFA) but lower saturated (SFA) and monounsaturated (MUFA) FA than postnatal infants' plasma. SFA decreased with age in the infants, but MUFA and linoleic acid (LA, 18:2omega6) increased. LCPUFA were lower in the plasma of 5-day-old infants than in cord blood, but LA was 80%, alpha-linolenic acid (ALA, 18:3omega3) 33% and the ratio omega-6/omega-3 42% higher. At day 42, LA increased further, LCPUFA remained similar, and was in breast milk lower than at day 5, while ALA and gamma-linolenic acid (18:3omega6) were higher. The activity index of desaturases indicated high Delta9 activity in breast milk and high activity of Delta5 desaturase in the infants. CONCLUSION: Breast milk FA composition changed markedly from day 5 to 42 with increasing correlation to infants' plasma. Calculation of desaturase activities suggested high capacity of LCPUFA synthesis.

Dornase alfa is well tolerated: data from the epidemiologic registry of cystic fibrosis.

After closure of the Epidemiologic Registry of Cystic Fibrosis (ERCF), a comprehensive safety analysis of dornase alfa was performed. A planned subanalysis focused on children under 5 years old. Reported serious adverse events (SAEs) were assigned a preferred term and ascribed to a specific organ system. Possible serious adverse reactions to dornase alfa (SADRs) were identified by reporting clinics. Twenty-eight of 15,865 SAEs (0.18%), occurring in 26 of 6,829 patients ever treated with dornase alfa (0.38%), and no deaths were reported as possible SADRs: most were typical complications of cystic fibrosis (CF). There was no evidence of any unrecognized risk of treatment. During 24,586 patient-years of follow-up (FU) of ever-treated patients, SAEs (mostly typical respiratory complications of CF) were more frequent on-treatment (0.4999/patient-year; 95% CI 0.4921-0.5076) than off-treatment (0.3889; 0.3787-0.3992). This was likely caused by within-patient prescription bias. During 655 patient-years of FU in 328 ever-treated patients under 5 years old, SAEs (mostly pulmonary exacerbations of CF) were slightly less frequent during treatment: 0.2911 (0.2367-0.3455) versus 0.3563 (0.3086-0.4040; ns). Results confirm the safety of dornase alfa in CF patients of all ages. Children under 5 years old tolerate dornase alfa at least as well as older patients.

Swedish pre-school children eat too much junk food and sucrose.

AIM: To analyze dietary intake in healthy 4-year-old children. METHODS: Families from three Paediatric Health Care Centres in different socio-economic areas in Göteborg completed 7-day food records and questionnaires about socio-economy. RESULTS: One hundred thirty two/153 completed the study, 49% of parents were university educated. Eighteen percent of children were overweight/obese. Energy intake was high; 67% had sucrose intake exceeding Nordic Nutrition Recommendations (NNR) but 36% had n-3 fatty acid intake < 0.5 energy percent. Significant negative correlations were found between sucrose and fat and between BMI and fat intake. Junk food supplied 24% of energy. Ninety-two percent had low vitamin D intake, 70% low iron and 21% low calcium intake. Gruel, which was consumed by 28%, had a positive impact on micronutrient intake. Child care and mother's origin seemed to influence dietary intake. CONCLUSION: In 4-year olds from well-educated urban families, 18% was overweight/obese. Total energy intake was above present NNR but lower than 20 years ago, when overweight was rare. Fat energy intake was negatively associated with BMI, and low n-3 fatty acid intake was associated with higher body weight. In several aspects dietary intake was not optimal in the children.

Perinatal essential fatty acid deficiency influences body weight and bone parameters in adult male rats.

Fetal and postnatal nutrition have long-term effects on the risk for development of diseases late in life in humans and animals. The aim of the present study was to investigate the effect of dietary deficiency of essential fatty acids (EFA) in the perinatal period on later body weight and bone mass. During late gestation and throughout lactation, rats were fed a control or an EFA-deficient (EFAD) diet. At 3 weeks of age the offspring were weaned onto an ordinary chow and followed until adult age. The mean body weight of adult rats receiving the EFAD diet during the perinatal period was significantly increased from 12 weeks of age compared to the controls (P<0.05). Analysis by peripheral quantitative computerized tomography (pQCT) at 44 weeks of age showed that the trabecular volumetric bone mineral density (BMD) of the femur was significantly decreased (P<0.05) but the cortical bone mineral content, cortical area, and cortical thickness were increased (P<0.05) in the EFAD group of rats. The length of the femur was not affected. In conclusion, neonatal EFA deficiency was in adult rats associated with increased body weight and significant changes in both cortical and trabecular bone. The results indicate that regulatory mechanisms related to bone mass seemed to be programmed by EFA in the perinatal period. The nature of this modulation needs to be identified.

Dietary n-6:n-3 fatty acid ratio in the perinatal period affects bone parameters in adult female rats.

PUFA and their metabolites are important regulators of bone formation and resorption. The effect of PUFA on bone growth may be especially striking during the perinatal period. The aim of the present study was to investigate the effect of diets with different n-6:n-3 fatty acid (FA) ratios during the perinatal period on bone parameters in the adult offspring. During late gestation and throughout lactation, rat dams were fed an isoenergetic diet containing 70 g linseed oil (n-3 diet), soyabean oil (n-6+n-3 diet) or sunflower-seed oil (n-6 diet) per kg with n-6:n-3 FA ratios of 0.4, 9 and 216, respectively. The offspring were weaned onto an ordinary chow and followed until 30 weeks of age. Bone parameters were analysed using peripheral quantitative computerised tomography and dual-energy X-ray absorptiometry. Femur length and cortical cross-sectional bone area and bone mineral content were significantly higher in the n-6+n-3 group than in the other groups. Cortical bone thickness in the n-6+n-3 group was increased compared with the n-3 group, but most cortical bone parameters did not differ between the n-3 and n-6 groups. The results suggest that regulatory mechanisms were influenced by the n-6:n-3 FA ratio early in life and not compensated for by the introduction of an ordinary diet after weaning.

The ratio of n-6 to n-3 fatty acids in maternal diet influences the induction of neonatal immunological tolerance to ovalbumin.

Prevalence of allergy is increasing in many countries and might be related to changed environmental factors, such as dietary fatty acids (FA). The present study investigates whether dietary ratio of n-6 to n-3 FA influences the induction of immunological tolerance to ovalbumin (OA) in neonatal rats. During late gestation and throughout lactation Sprague-Dawley rats were fed a diet containing 7% linseed oil (n-3 diet), sunflower oil (n-6 diet) or soybean oil (n-6/n-3 diet). At 10-16 days of age the rat offspring were subsequently exposed, or not, to OA via the milk. The offspring were weaned onto the same diets as the mothers and immunized with OA and the bystander antigen human serum albumin (HSA). In the offspring on the n-3 diet exposure to OA via the milk resulted in lower delayed type hypersensitivity reaction (DTH) and antibody responses against both OA and HSA, compared to those in the offspring not exposed to OA, indicating the induction of oral tolerance. In the offspring on the n-6 diet, the exposure to OA led to depressed specific immune responses against only OA, not HSA. In the offspring on the n-6/n-3 diet oral exposure to OA did not influence immune responses against OA, or HSA. The results indicate that the dietary ratio of n-6/n-3 FA is important for the induction of neonatal oral tolerance. Thus nonoptimal feeding may have effects on the development of immunological tolerance to dietary antigen ingested by the mother. The ratio of n-6/n-3 FA in the diet may be considered in the context of increased prevalence of allergy.

Duodenogastric bile reflux is common in cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) have a high incidence of gastroesophageal reflux disease, but few cases of mucosal injury are reported. Duodenogastric reflux has not been studied in CF but has been suggested to have a pathogenic role in producing alkaline injury to the esophageal mucosa. The aim of this study was to analyze the presence of duodenogastric reflux in patients with CF. PATIENTS AND METHODS: Ten patients with CF and 7 healthy volunteers participated in the study. Gastroduodenal manometry and intragastric perfusion were performed in all subjects. Gastric perfusate was analyzed for bilirubin and bile acids. Only patients and controls exhibiting normal migrating motor complexes were evaluated. RESULTS: Eight patients with CF had normal motility recordings and had significantly higher gastric bilirubin levels compared with healthy subjects (P = 0.003). The bilirubin concentration was associated with bile acid regurgitation in five patients with CF. All bile acids were conjugated with a high glycine/taurine ratio and low levels of secondary bile acids. Small amounts of keto bile acids were found in two patients. CONCLUSION: The patients with CF had an increased incidence of duodenogastric reflux compared with healthy subjects. The bile acid composition was typical for CF with low levels of secondary bile acids. Although high bile acid concentration was found in the duodenogastric reflux in most patients with CF, the less toxic profile of the bile acids might possibly contribute to the low frequency of Barrett's esophagus in CF.

Severe hypercholesterolaemia leads to strong Th2 responses to an exogenous antigen.

Severe hypercholesterolaemia is associated with decreased levels of immunoglobulin G2a (IgG2a) antibodies [T-helper 1 (Th1) response] to modified malondialdehyde-modified low-density lipoprotein (MDA-LDL) and increased levels of Th2-dependent IgG1 antibodies in apolipoprotein E-deficient (apoE(-/-)) mice. To investigate whether this reflects a general pattern of metabolic regulation of the humoral immune response, apoE(-/-) mice were fed diets resulting in different degrees of hypercholesterolaemia and immunized with keyhole limpet haemocyanin (KLH) in aluminium hydroxide. Cholesterol levels for different treatment groups ranged from 14 to 77 mmol/l in serum and from 10 to 39 mmol/g in liver. Mice with severe hypercholesterolaemia had increased IgG1 antibodies to MDA-LDL and decreased IgG2a anti-MDA-LDL. Importantly, titres of IgG2a antibodies to KLH were also decreased, while IgE anti-KLH was increased, with a corresponding induction of interleukin-4 (IL-4) and IL-10 and a decrease in interferon-gamma (IFN-gamma) in KLH-stimulated spleen cells in vitro. Thus, hypercholesterolaemia clearly affects antibody production both to the autoantigen MDA-LDL and to the exogenous antigen KLH, favouring antibody isotypes (IgG1 and IgE) that are dependent on Th2 help to B cells. Nuclear receptors ligated by oxidized lipid derivatives modulate T-cell responses, and it is speculated that this mechanism may cause the switch to Th2 in severe hypercholesterolaemia.

Association between serum oncofetal antigens CA 19-9 and CA 125 and clinical status in patients with cystic fibrosis.

UNLABELLED: In cystic fibrosis (CF), mucus plugging in the airways and in the gastrointestinal tract leads to severe morbidity and mortality. The mucin-associated antigens CA 19-9 and CA 125 are markers of gastrointestinal malignancy, and CA 19-9 has also been reported in association with pulmonary function in CF. AIM: To test whether these antigens might serve as markers for the severity of pulmonary and gastrointestinal disease in CF. METHODS: In 99 patients, aged 1 to 48 y, serum levels of CA 19-9 and CA 125 were measured by RIA and ELISA and related to clinical data. RESULTS: Patients with severe mutations had significantly increased serum levels of CA 125, indicating an association with a more severe CF phenotype. This was further supported by the association with lung function, chronic pulmonary colonization of Pseudomonas aeruginosa and pancreatic insufficiency. CA 19-9 was also shown to be associated with lung function and Ps. aeruginosa colonization. No gastrointestinal malignancy was found in our patients despite very high values of CA 19-9 in some patients. During a 5-y follow-up, the very high serum levels of CA 19-9 decreased along with improved general condition of the patients. CONCLUSION: Increased serum levels of CA 125 in CF patients were associated with severe cystic fibrosis transmembrane conductance regulator mutations and a severe phenotype. Both antigens were associated with pseudomonas colonization and lung function and CA 125 also with pancreatic insufficiency. The estimates of CA 19-9 are hampered by the influence of the Lewis histo-blood group system on the synthesis of CA 19-9.

Dornase alfa in the treatment of cystic fibrosis in Europe: a report from the Epidemiologic Registry of Cystic Fibrosis.

Dornase alfa (Pulmozyme) treatment for patients with cystic fibrosis (CF) has been shown to improve pulmonary function and reduce exacerbations of infection in a number of placebo-controlled double-blind studies. Data in the Epidemiologic Registry of Cystic Fibrosis (ERCF) in November 1998 were used to assess the long-term effectiveness in routine clinical practice of dornase alfa in terms of pulmonary function and frequency of acute pulmonary exacerbations in CF. At that time, the ERCF contained data on 13,684 CF patients, with a mean observation period of 2.3 years. To be included in the analysis, patients had to have 2 years of data in the Registry in appropriate detail. Overall, untreated patients showed a decline in forced expiratory volume in 1 sec over a 2-year period of -2.3% predicted, but treated patients were stable, showing a change of 0.3% predicted, i.e., a treatment benefit of 2.5%. Compared to untreated patients, there were 25 fewer exacerbations per 100 treated patients per year. The analysis suggested that younger patients were likely to benefit more from treatment. The findings of randomized clinical trials were supported by the data collected in routine clinical practice.

Decreased bone mineral density in normal-growing patients with cystic fibrosis.

AIM: To study bone mineral density (BMD) in normal-growing patients with cystic fibrosis (CF) and its relation to clinical and biochemical markers of nutrition and lung function. METHODS: Seventy consecutive patients aged 6-49 y with CF were investigated using dual X-ray absorptiometry and the findings related to anthropometric data. Energy intake was calculated and basal metabolic rate and serum values for calcium, phosphorus, calcitonin and 25(OH) calcidiol measured. Working capacity, lung function and pseudomonas colonization were determined as parameters of physical fitness and severity of pulmonary disease. RESULTS: The average z-score of BMD was decreased in the lumbar spine in both children and adults, being -0.7 +/- 1.0 and -0.5 +/- 1.0, respectively, as was the femoral neck BMD z-score, being -0.3 +/- 0.9 and -1.1 +/- 1.0 for children and adults, respectively. BMD was correlated to lung function and working capacity, but not to anthropometric data at multiple regression analysis compensating for age and calcitonin. No correlation was found with energy intake, basal metabolic rate or biochemical markers, with the exception of calcitonin. CONCLUSION: BMD z-scores were significantly lower than those in the normal population despite normal anthropometry. Osteoporosis was rare. The strongest correlation was found with lung function. Our data indicate that BMD at all ages might be a sensitive indicator of the general status of patients with CF.