Biomedical subjects
Publications and source records attributed to B Koletzko.
Explore the source record for details and available documents.
A case is reported of a 14 month old boy with severe dietary vitamin B-12 deficiency caused by his mother's vegan diet. Clinical, electroencephalography (EEG), and haematological findings are described. Cranial magnetic resonance imaging (MRI) showed severe frontal and frontoparietal cranial atrophy. Vitamin B-12 supplements led to a rapid improvement of haematological and neurological symptoms. Serum vitamin B-12 and urinary methylmalonate excretion were normal 10 days after treatment began. After six weeks, EEG was normal and cranial MRI after 10 weeks showed complete disappearance of all structural abnormalities. Cognitive and language development, however, remained seriously retarded at the age of 2 years. It is concluded that infantile vitamin B-12 deficiency induced by maternal vegan diets may cause lasting neurodisability even though vitamin B-12 supplementation leads to rapid resolution of cerebral atrophy and electroencephalographic abnormality.
Previous studies on human colorectal tumor protein synthesis in situ relied on techniques that required intra- or perioperative sampling to obtain a sufficient biopsy size. The purpose of the present study was to develop a new technique by use of new mass spectrometry equipment [capillary gas chromatography (GC)-combustion isotope ratio mass spectrometry (IRMS)], which allows reduction of the necessary sampling size. Thereby, tumor sampling could be done via conventional rectosigmoidoscopy, excluding the need for further disturbing invasive measures. Fifteen postabsorptive patients with localized rectal cancer received a primed-constant infusion of [1-13C]leucine (0.16 mumol.kg-1.min-1 constant, 9.6 mumol/kg prime). Forceps biopsies were taken after 3 and 6 h. In five subjects, tumor tissue and normal mucosa were studied simultaneously. Determination of protein-bound leucine enrichment was done by GC-IRMS, and GC-quadrupole MS was used to determine tracer-to-tracee ratios (tracer/tracee) for free intracellular leucine. GC-MS data demonstrated achievement of a steady state in the precursor pool enrichment after 3 h of isotope infusion (tracer/tracee at 3 h: 6.34 +/- 0.46%, at 6 h: 6.58 +/- 0.38%). Calculation of tumor protein synthesis yielded a fractional synthetic rate (FSR) of 1.06 +/- 0.11%/h or 25.5 +/- 2.6%/day (range 12.0-37.1%/day). At any time, protein-bound leucine enrichment was significantly higher in tumor tissue than in normal mucosa of the same subject. However, protein synthetic rates were comparable (tumor: 1.09 +/- 0.20%/h, mucosa: 1.29 +/- 0.28%/h). Thus combined GC-combustion IRMS and GC-/quadrupole MS provide a simple, reliable, and minimally invasive method to determine tumor FSR in situ, thereby excluding interferences common to previous methods. Tumor and mucosa tissues are similar with respect to protein synthesis, but they apparently differ with respect to leucine extraction from the arterial blood.
A high intake of trans fatty acids in children may be disadvantageous because of untoward effects on lipoprotein metabolism and a possible impairment of arachidonic acid synthesis. We measured the trans fatty acid content of different brands of spreads and cold cuts typically consumed by German children because these foods may contribute a considerable portion of total trans fatty acid intake. The highest trans fatty acid contents were found in regular margarines (4.5, 0.0-10.6; median %-wt/wt of fatty acids, minimal-maximal), chocolate spreads (5.5, 0.7-11.1), butter (4.7, 3.7-5.2) and cheese (3.6, 1.8-4.0), while lower values were present in diet margarines (0.2, 0.0-0.4), vegetarian spreads (0.2, 0.1-0.4), peanut butter (0.0, 0.0-0.3) and sausages (1.7, 0.6-6.4). Calculations of typical dietary plans for young children show that food selection and variations in trans fatty acid contents may lead to marked differences in daily trans intake of > 100% (3.1 g/d vs. 1.5 g/d). We propose that trans fatty acid content should be declared on labels of fatty food products to enable the consumer to choose, and further attempts should be made to lower trans fatty acid formation during technical hydrogenation.
Infants need arachidonic acid (AA; C20:4n-6) for eicosanoid synthesis and deposition in growing tissues, including brain. Human milk supplies preformed AA in amounts considered to meet accretion in membrane-rich tissues, but vegetable oil-based infant formulas do not contain AA. We studied two groups of ten healthy infants, each fed human milk or formula, and analyzed plasma lipid composition. Percentage contributions of AA to plasma phospholipids were stable over two months after birth in breast-fed infants, but infants fed formula developed significantly (P < 0.05) lower levels at the ages of two weeks (formula 6.9% vs. breast 9.4%, w/w), one month (6.2 vs. 9.1%), and two months (5.7 vs. 8.4%). In a second trial, we randomized infants to receive (from birth to age four months) formula without or with both AA and docosahexaenoic acid (DHA; C22:6n-3) at levels typical for mature human milk. Infants fed conventional formula showed a continuous decrease of phospholipid AA over time, whereas feeding of formula supplemented with AA and DHA led to significantly higher AA levels, similar to those in breast-fed infants (two months: supplemented 9.6% vs. unsupplemented 7.1%; four months: 8.7 vs. 6.6%). In order to estimate infantile capacity for endogenous synthesis of AA, we fed four term neonates with newly diagnosed phenylketonuria (mean age 18 d) a formula with all fat contributed by corn oil, which has a higher natural 13C-enrichment than European human milk or formula. Analysis of 13C-enrichment in plasma fatty acids over four days allowed us to estimate infantile AA synthesis. We found an increased 13C-value in plasma AA of all infants, which indicates that term neonates can synthesize AA. However, with a simplified isotope balance equation, we estimate that endogenous synthesis contributed only about 23% of total plasma arachidonic acid by day four. We conclude that full-term infants fed formula may require a dietary supply of some preformed AA if the biochemical status of breast-fed infants is to be achieved.
Fatty acid composition of plasma phospholipids (PL), triglycerides (TG), and sterol esters (STE) was determined by high-resolution capillary gas-liquid chromatography in 22 obese children (age: 13.7 +/- 1.4 y, body weight relative to normal weight for height: 170 +/- 24%, mean +/- SD) and compared with data obtained in 25 age-matched healthy controls. There were no differences in the levels of linoleic acid (LA, C18:2n-6) in any of the plasma fractions from obese children and the controls. Obese children exhibited significantly higher values of arachidonic acid (AA, C20:4n-6) than controls both in PL (12.6 [2.4] vs. 8.3 [1.4], % wt/wt, [median (interquartile range)], P < 0.001) and STE (7.3 [1.8] vs. 6.0 [1.1], P < 0.05). Similarly, obese children showed higher values than controls for dihomo-gamma-linoleic acid (DHGLA, C20:3n-6) in PL (4.0 [0.5] vs. 3.0 [0.6], P < 0.001), TG (0.4 [0.1] vs. 0.2 [0.1], P < 0.001), and STE (0.9 [0.1] vs. 0.7 [0.1], P < 0.01), and for gamma-linolenic acid (C18:3n-6) in STE (1.1 [0.2] vs. 0.8 [0.2], P < 0.001). The AA/LA ratios were higher in obese children than in controls in PL (0.68 [0.16] vs. 0.42 [0.09], P < 0.0005) and STE (0.16 [0.04] vs. 0.12 [0.02], P < 0.05), whereas the AA/DHGLA ratios were lower in TG of obese children than in controls (3.40 [0.64] vs. 5.10 [1.75], P < 0.005). Plasma glucose concentrations were inversely related to AA in TG (r = 0.53, P < 0.05), and plasma TG concentrations were inversely related to AA in PL and STE (r = -0.49, P < 0.05 and r = -0.48, P < 0.05) and to the AA/DHGLA ratios in PL (r = -0.57, P < 0.01), TG (r = -0.56, P < 0.01), and STE (r = -0.56, P < 0.01). We conclude that the significantly higher values of n-6 long-chain polyunsaturated fatty acids (LCP) in plasma lipids of obese children than in age-matched controls may be caused by an enhanced activity of delta 6-desaturation, and we speculate that elevated fasting immunoreactive insulin seen in obese children (19.4 +/- 8.0 microU/mL) may stimulate synthesis of n-6 LCP fatty acids.
We have previously reported appreciable concentrations of hydrogen sulfide (H2S) in paediatric amino-acid solutions, apparently formed from cysteine during the production process. Since manufacturers assured us of their aim to reduce the contents of the potentially toxic H2S in these solutions, we determined whether lower amounts have been achieved 2 years after our first report. Median H2S content of 13 paediatric amino-acid solutions was 22.8 microg/l (range: not detectable to > 280 microg/l which is comparable to the amounts previously found. Median H2S content of 8 special solutions for renal and hepatic disorders was 15.8 microg/l (range not detectable to > 280 microg/l). We conclude that manufacturers should make further efforts to reduce H2S amounts in parenteral amino-acid solutions.
Plasma concentrations of alpha-tocopherol and retinol were measured in 17 obese children (10 boys and 7 girls, age: 13.9 +/- 0.3 y, mean +/- s.e.m.) and related to anthropometric indices and fasting plasma insulin concentrations. Body weight was 89.0 +/- 5.3 kg, relative body weight 165 +/- 6%, body fat content 38.9 +/- 1.2% and body mass index 32.3 +/- 1.3 kg/m2. Plasma alpha-tocopherol, retinol and insulin concentrations were 18.5 +/- 1.6 mul/l, 2.0 +/- 0.2 mu/l and 17.2 +/- 1.6 mU/l, respectively. Neither alpha-tocopherol nor retinol concentrations were related to age. Plasma retinol concentrations were positively correlated to weights (r = 0.60, P = 0.01) and heights (r = 0.65, P < 0.01), but not to body fat contents. In contrast, plasma alpha-tocopherol concentrations were not related to weights and heights, but a significant inverse relation was seen to body fat contents (r = -0.49, P = 0.04). Fasting plasma insulin concentrations did not correlate with plasma retinol values, but were inversely related to plasma alpha-tocopherol concentrations (r = -0.53, P = 0.02) and alpha-tocopherol: cholesterol+triglyceride ratios (r = -0.57, P = 0.01). These results indicate that the factors influencing the availability of retinal and alpha-tocopherol in obese children may be different.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
13C-urea breath tests were sampled in 51 subjects with an isotope-selective non-dispersive infrared spectrometer (NDIRS) and compared with the results of conventional isotope-ratio mass-spectrometry (IRMS). Delta-over-baseline values of both methods correlated well (r = 0.976 at 15 min and 0.985 at 30 min, both p < 0.0005). With a cut-off for delta-over-baseline values of 5/1000 (i. e., 5 per thousand), both methods correctly classified all 36 Helicobacter-pylori-negative and all 15 H-pylori-positive subjects. All infected subjects had values over 11/1000 in all samples with both methods. NDIRS is of equal value as IRMS for the diagnosis of H pylori infection. Because NDIRS gives on-line results and is easier and cheaper, we consider NDIRS useful for clinical practice.
The objective was to determine whether rats could synthesize longer chain polyunsaturates from hexadecadienoate (16:2n-6) and hexadecatrienoate (16:3n-3). Rats were gavaged with uniformly 13C-labelled hexadecadienoate or hexadecatrienoate, euthanized 24 h later, and total lipids were extracted from liver and carcass. Gas chromatography/combustion/isotope ratio mass spectrometry was used to measure 13C levels in individual liver, carcass, and whole body fatty acids. 13C Enrichment was present in desaturated and chain-elongated polyunsaturates, including linoleate, arachidonate, alpha-linolenate, and docosahexaenoate at 12-13% of the dose of tracer given. 13C Enrichment from hexadecatrienoate was highest in carcass and liver alpha-linolenate, representing 3.5 and 17.9% of the total alpha-linolenate pool, respectively. For linoleate, arachidonate, or docosahexaenoate, the contribution of 13C did not exceed 0.2% of the total body pool. Green leafy vegetables common in the human diet were shown to contain up to 1.2% of total fatty acids as hexadecadienoate and 11.6% as hexadecatrienoate. Hence, humans consuming green vegetables probably synthesize a small proportion of their total body content of linoleate and alpha-linolenate.
Fatty acids in plasma phospholipids were studied in 35 severely malnourished young children with a median age of 29 mo (range: 9-43 mo), who were either seronegative for human immunodeficiency virus-1 (HIV) (n = 16) or suffered from asymptomatic (stage P-1; n = 12) or symptomatic (stage P-2; n = 7) HIV disease. The malnourished children had significantly lower percentages (% by wt) of phospholipid arachidonic (20:4n-6, AA) and docosahexaenoic (22:6n-3, DHA) acids than 25 age-matched healthy control subjects (AA: 7.05% and 8.70% by wt; DHA: 0.92 and 2.61% by wt, P < 0.001). Body weights of malnourished children did not correlate with linoleic (18:2n-6) and alpha-linolenic (18:3n-3) acid values but were significantly and positively correlated with AA and DHA values (r = 0.40, P = 0.02 and r = 0.63, P < 0.0001, respectively). Plasma concentrations (mg/L) of total phospholipid fatty acids did not differ among seronegative, stage P-1, or stage P-2 patients. Percentage contributions of AA and eicosapentaenoic acid (20:5n-3, EPA) did not differ among those seronegative or in stages P-1 and P-2. In contrast, values of dihomo-gamma-linolenic acid (20:3n-6) were significantly (P < 0.05) lower in stage P-2 (2.38 mg/L) than in either seronegative (3.47 mg/L) or stage P-1 (3.66 mg/L) patients. We conclude that the severely malnourished children developed a depletion of both AA and DHA proportional to the degree of malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)
Neonates need arachidonic acid (AA) for their growing tissues, but it is unknown to what extent they can synthesize AA from dietary linoleic acid (LA). We studied infantile AA synthesis by using different natural 13C amounts in dietary fats. The diets of four infants ages 18 +/- 4 days (mean +/- SD) with newly diagnosed phenylketonuria were changed from breast milk or formula to a phenylalanine-free diet with corn oil as the only fat source. Compared with most dietary fats in Europe derived from C3 plants, corn oil LA has a higher 13C content. We determined the 13C content of LA and AA in 0.25-0.5 ml serum before and for 3-4 days after the diet change with gas chromatography combustion isotope ratio mass spectrometry (GC-IRMS). Baseline delta 13C values were -31.5 +/- 1.1% (mean +/- SD) for serum LA and -30.1 +/- 1.2% for AA. The corn oil diet induced changes of delta 13C values over baseline in LA of 8.9 +/- 1.0 on day 1 and 12.7 +/- 0.7 on day 4, respectively. The changes of AA delta 13C values were 0.5 +/- 0.7 and 2.7 +/- 0.7 on days 1 and 4. We conclude that reproducible detection of differences in delta 13C values of fatty acids in small samples of infantile serum, induced by dietary variation of natural 13C amounts, is feasible with GC-IRMS. Since the corn oil diet did not contain AA, the observed change of AA delta 13C shows active endogenous AA synthesis in full-term neonates.(ABSTRACT TRUNCATED AT 250 WORDS)
Long-chain (LC) polyunsaturated fatty acids (PUFA) (LCP) are considered conditionally essential nutrients for low birth weight infants (LBWI). Therefore, enrichment of LBWI formulae with metabolites both linoleic (omega-6) and alpha-linolenic (omega-3) acids at levels typical for human milk has been recommended. However, previous feeding trials with LCP-enriched formulae evaluated only a dietary supplementation with omega-3 LCP from fish oils alone or with both omega-3 and omega-6 LCP at levels considerably lower than usual human milk contents. We studied the effects of an LBWI formula providing the major omega-3 and omega-6 LCP, docosahexaenoic and arachidonic acids, in amounts similar to those in average human milk. Twenty-seven LBWIs were enrolled in this study when they tolerated full enteral feeding (> or = 130 ml milk/kg/day). Infants either received their own mother's milk (n = 8, birthweight 1218 +/- 146 g, gestational age 30.2 +/- 1.5 weeks, mean +/- SD) fortified with protein and minerals (FM-85, Nestle Ag, Munchen, Germany; dosage 5 g/100 ml milk) or were randomly assigned to blinded batches of an LBWI formula (Prematil, Milupa AG, Friedrichsdorf, Germany) without LCP (n = 10, 1280 +/- 229 g, 31.1 +/- 3.1 weeks) or with LCP (n = 9, 1253 +/- 334 g, 30.4 +/- 3.3 wks.). During the study period of 21 days, the three feeding groups did not differ in growth and feeding tolerances as assessed by occurrence of gastric residuals, spitting, or abdominal distention; however, firms stools were noted more frequently in the two formula groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary damage in cystic br osis (CF) is associated with chronic inflammation mediated in part by proinflammatory 5-lipoxygenase products (5-LOP, leukotrienes and 5-hydroxyeicosatetraenoic acid) from polymorph neutrophil granulocytes (PMN). The authors studied 5-LOP formation of PMN from CF patients and in vitro effects of added eicosapentaenoic acid (EPA) and fish oil. Circulating PMN were isolated from 10 CF patients without acute infections and 10 control persons of the same age (4-20 years). Total 5-LOP liberation from PMN of CF patients was significantly increased over controls after incubation with the calcium ionophore A23 (1 mumol L-1) without arachidonic acid (AA) (380 +/- 24 vs. 294 +/- 28 pmol mL-1) and with 10 mumol L-1 AA (1303 +/- 104 vs. 1015 +/- 104 pmol mL-1), and there were nonsignificant trends to high values after incubation with 5 mumol L-1 platelet activating factor (PAF, 134% of controls) and 1 mumol L-1 formyl-methionylleucyl-phenylalanine (FMLP, 125%). The addition of 100 micrograms mL-1 fish oil to PMN of CF patients challenged with A23 completely suppressed synthesis of proinflammatory 5-LOP of the 4-series, while inactive 5-LOP metabolites of the 5-series were produced. Added EPA (10 mumol L-1) also suppressed 4-series 5-LOP and significantly reduced leukotriene B4 concentration by 48% from 39.9 +/- 3.2 to 20.6 +/- 11.4 pmol L-1, again with a concomittant increase of inactive 5-series metabolites. The authors conclude that the turnover of endogenous and exogenous AA is enhanced in CF, possibly due to stimulated phospholipase A2 activity. The relatively small effect of the receptor dependent stimuli PAF and FMLP may be caused by a down-regulation of PMN receptors in CF. Supplementation of long-chain omega-3-fatty acids may be beneficial for reducing excessive inflammation in CF patients and should be further evaluated.
Full-term infants fed formula without dietary long-chain polyunsaturated fatty acids (LCF) exhibit significantly lower plasma LCP values than breast-fed infants. We studied prospectively two groups of healthy full-term infants fed conventional infant formula without LCP (F, n = 10) or the same formula enriched with both omega-6 and omega-3 LCP (LCP-F, n = 12). Anthropometric data were obtained and fatty acid (FA) compositions of plasma phospholipids, triglycerides and sterol esters as well as plasma retinol and alpha-tocopherol concentrations were determined at 5 days and 1, 2, 3 and 4 months of age. Gains in weight, length and head circumference did not differ between the two groups throughout the study period. Plasma FA values did not differ at 5 days of age. Between 1 and 4 months of age, plasma phospholipids of infants fed LCP-F consistently had significantly (p < 0.05) higher percentages of arachidonic acid (1 month: 9.7 (0.8) versus 7.0 (1.3) %wt/wt, 4 months: 8.7 (0.5) versus 6.6 (1.0) %wt/wt, median (interquartile range), LCP-F versus F) and docosahexaenoic acid (1 month: 2.9 (0.5) versus 1.6 (0.3) %wt/wt; 4 months: 2.9 (0.4) versus 0.9 (0.3) %wt/wt). Plasma retinol and alpha-tocopherol concentrations did not differ between the two groups throughout the study. We conclude that this form of LCP enrichment of formula for full-term infants effectively enhances plasma LCP contents without detectable adverse effects. The potential effects on functional outcome need to be studied carefully in prospective clinical trials.
To determine the biochemical effects of the fatty acid composition of plasma lipids, two groups of 10 healthy full term infants who were either exclusively breast fed or received a formula with similar contents of linoleic and alpha linolenic acids, but without long chain polyunsaturated (LCP) fatty acids, were studied prospectively. Plasma phospholipid, triglyceride, and sterol ester fatty acids were determined at the age of 2, 4, and 8 weeks by high resolution capillary gas chromatography. Breast fed infants maintained stable LCP fatty acid concentrations throughout the study. Formula fed infants had significantly lower median values of arachidonic acid (AA) at the ages of 2 (6.9 v 9.5% wt/wt) and 4 weeks (5.9 v 7.9%) and docosahexaenoic acid (DHA) at the ages of 4 (1.1 v 1.7%) and 8 weeks (1.0 v 1.7%) in plasma phospholipids. Median AA values in triglycerides were also significantly lower in the infants receiving formula at the ages of 2 (0.4 v 0.6%) and 4 weeks (0.3 v 0.6%). It is concluded that formula fed full term infants are unable to match the omega-3 and omega-6 LCP status of breast fed full term infants until at least two months after birth.