Effect of n-3 polyunsaturated fatty acids in asthma after low-dose allergen challenge.

BACKGROUND: We investigated the anti-inflammatory potential of n-3 polyunsaturated fatty acids (PUFA) on specific bronchial inflammation. Allergic asthmatics were challenged using a low-dose allergen provocation model. METHODS: Our parallel double-blinded study randomly assigned 23 house dust mite-allergic asthmatics (aged 22-29 years; 13 females, 10 males) to dietary supplementation with either an n-3 PUFA-enriched fat blend (0.69 g/day) or placebo for 5 weeks. After 3 weeks, the patients were challenged daily with low doses of mite allergen for 2 weeks. Primary outcome parameters were effects on lung function (forced expiratory volume in 1 s, FEV(1)) and exhaled nitric oxide (eNO) as a marker of bronchial inflammation. RESULTS: Even before the bronchial challenge, eNO was significantly lower in the n-3 PUFA group (p=0.014). Levels of eNO increased during allergen exposure in both groups, but differences in means were significantly lower in the n-3 PUFA group (p=0.022). During the low-dose allergen challenge, there were no differences between the groups with regard to symptoms, FEV(1) or the allergen dose required to induce deterioration of lung function (PD(20)). Numbers of sputum eosinophils did not differ significantly, while serum eosinophils (10.1+/-0.1.84 vs. 5.79+/-0.69%) as well as changes in eosinophilic cationic protein (20.5+/-9.93 vs. -1.68+/-4.36 ng/ml) and in vitro cysteinyl leukotriene release (2,889+/-872 vs. 1,120+/-173 ng/ml) were significantly lower in the n-3 PUFA group (p<0.05 each). CONCLUSION: Our results provide evidence that dietary supplementation with n-3 PUFA is able to reduce bronchial inflammation even after low-dose allergen challenge.

Dietary long-chain polyunsaturated fatty acid supplementation in infants with phenylketonuria: a randomized controlled trial.

BACKGROUND: Pre- and postnatal tissue accretion of long-chain polyunsaturated fatty acids (LCPUFA) has been related to visual and cognitive development in healthy children in several studies. Children with phenylketonuria (PKU) consume diets with very low contents of preformed LCPUFA. We studied prospectively the LCPUFA status in infants with PKU without or with LCPUFA supplementation during the first year of life. SUBJECTS AND METHODS: Infants with PKU were enrolled at diagnosis (<4 weeks of age) and randomized double blind to phenylalanine-free amino acid supplements without LCPUFA (n = 11) or with both arachidonic (AA, 0.46 wt%) and docosahexaenoic acids (DHA, 0.27 wt%) (n = 10). At enrolment and again at 1, 2, 3, 4, 6, 9 and 12 months, plasma phospholipid fatty acids were measured and dietary intakes were calculated from dietary protocols. RESULTS: Unsupplemented patients showed a marked LCPUFA depletion to levels clearly below those observed in healthy breast-fed infants. In contrast, supplemented infants had stable and higher LCPUFA levels than unsupplemented infants, reaching significant differences for AA values at 3, 4 and 6 months, and for DHA values at 1, 3, 4, 6, 9 and 12 months. Plasma phospholipid levels correlated closely with estimated dietary intakes of preformed LCPUFA. CONCLUSION: Low LCPUFA intakes with PKU diets induce marked depletion of AA and particularly of DHA in the first year of life. Thus endogenous synthesis of LCPUFA from precursors supplied by diet seems unable to compensate for low LCPUFA intakes. LCPUFA supplementation of PKU diets during the first year of life effectively enhances LCPUFA status to levels comparable to those of healthy breast-fed infants.

alpha-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes.

OBJECTIVE: We examined the effect of lipoic acid (LA), a cofactor of the pyruvate dehydrogenase complex (PDH), on insulin sensitivity (SI) and glucose effectiveness (SG) and on serum lactate and pyruvate levels after oral glucose tolerance tests (OGTTs) and modified frequently sampled intravenous glucose tolerance tests (FSIGTTs) in lean (n = 10) and obese (n = 10) patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: FSIGTT data were analyzed by minimal modeling technique to determine SI and SG before and after oral treatment (600 mg, twice a day, for 4 weeks). Serum lactate and pyruvate levels of diabetic patients after glucose loading were compared with those of lean (n = 10) and obese (n = 10) healthy control subjects in which SI and SG were also determined from FSIGTT data. RESULTS: Fasting lactate and pyruvate levels were significantly increased in patients with type 2 diabetes. These metabolites did not exceed elevated fasting concentrations after glucose loading in lean patients with type 2 diabetes. However, a twofold increase of lactate and pyruvate levels was measured in obese diabetic patients. LA treatment was associated with increased SG in both diabetic groups (lean 1.28 +/- 0.14 to 1.93 +/- 0.13; obese 1.07 +/- 0.11 to 1.53 +/- 0.08 x 10(-2) min-1, P < 0.05). Higher SI and lower fasting glucose were measured in lean diabetic patients only (P < 0.05). Lactate and pyruvate before and after glucose loading were approximately 45% lower in lean and obese diabetic patients after LA treatment. CONCLUSIONS: Treatment of lean and obese diabetic patients with LA prevents hyperglycemia-induced increments of serum lactate and pyruvate levels and increases SG.

Ketogenic effects of low and high levels of carnitine during total parenteral nutrition in the rat.

Male Wistar rats received total parenteral alimentation for 3 d. The animals were divided into three groups: group 1, without L-carnitine; group 2, 10 mg (62.1 mumol) L-carnitine X kg-1 X d-1; and group 3, 100 mg (621.1 mumol) L-carnitine X kg-1 X d-1. Fat oxidation was followed by indirect calorimetry. Maximal oxidative metabolism of fatty acids was achieved with supplementation of L-carnitine in small amounts (10 mg X kg-1 X d-1). This was demonstrated by a decrease of the RQ and of the serum concentrations of fatty acids and by an increase of beta-OH-butyric acid. Decreased liver free and long-chain acylcarnitine and increased short-chain acylcarnitine concentrations in this group also demonstrate an increased ketogenicity. This ketogenic effect of carnitine decreases when higher concentrations of carnitine are used. This study demonstrates that the ketogenic effect of carnitine is dose dependent.

Reversal of experimental essential fatty acid deficiency by cutaneous administration of safflower oil.

The intriguing observation that cutaneous application of essential fatty acid (EFA)-rich oil corrects the biochemical abnormalities of EFA deficiency was evaluated in EFA-deficient rats. Approximately 185 mg of safflower oil (140 mg of linoleic acid) were applied daily for 15 days to the kin of EFA-deficient rats. Before and after treatment with the safflower oil, the fatty acid patterns of plasma and erythrocyte phospholipid as well as of plasma triglyceride and cholesterol ester fractions were determined. The linoleic and arachidonic acid content of both plasma and erythrocyte phospholipid increased, while the eicosatrienoic acid content of both fractions decreased. The linoleic acid content of plasma triglyceride increased with safflower oil treatment, but little change occurred in the almost undetectable pretreatment levels of arachidonic and eicosatrienoic acid. In the plasma cholesterol ester fraction, arachidonic acid increased with treatment and eicosatrienoic acid decreased, but the small increase in the linoleic acid content was not statistically significant. Thus, the study confirms the observation that cutaneous application of EFA-rich oils reverses the plasma biochemical manifestation of EFA deficiency. In addition cutaneously applied EFA-rich oils reversed the biochemical manifestations of EFA deficiency in erythrocytes. Whether or not cutaneous application of such oils will prevent EFA deficiency, however, remains to be proven.

Correlation between long-chain acylcarnitine in serum and myocardium after heart transplantation in humans.

The concentrations of free, short-chain, and long-chain acylcarnitine were determined in 19 right ventricular endomyocardial biopsies and in serum from 14 patients after orthotopic heart transplantation and 3 nontransplanted control patients with normal cardiac function. Coronary angiography was normal in all patients. Left ventricular ejection fraction as measured by radionuclide ventriculography was not different between heart-transplanted and control patients (60.3 +/- 6.7% and 61.7 +/- 10.7%, respectively). Myocardial and serum carnitine concentrations in heart-transplanted patients were not different from control patients (myocardium: free carnitine 11.8 +/- 4.8 vs 7.1 +/- 7.1, short-chain acylcarnitine 4.5 +/- 2.1 vs 5.8 +/- 2.0, long-chain acylcarnitine 4.9 +/- 3.8 vs 3.9 +/- 3.2 mumol/g noncollagen protein; serum: free carnitine 32.6 +/- 11.2 vs 32.0 +/- 9.9, short-chain acylcarnitine 7.3 +/- 5.2 vs 5.1 +/- 1.3, long-chain acylcarnitine 4.1 +/- 2.7 vs 4.8 +/- 4.0 mumol/L). There was a highly significant correlation between myocardial and serum long-chain acylcarnitine (r = 0.76, P < 0.001). The data suggest that carnitine metabolism is not altered after heart transplantation.

Glutaryl-coenzyme A dehydrogenase deficiency: a distinct encephalopathy.

Clinical course, diagnostic and therapeutic management, and neurodevelopmental outcome were evaluated in 11 patients with glutaryl-coenzyme A dehydrogenase deficiency. In 9 patients macrocephalus was present at or shortly after birth and preceded the neurological disease. In 7 children an acute illness resembling encephalitis appeared after a period of normal development; 2 had developmental delay and progressive "dystonic cerebral palsy." Later, all 9 displayed typical signs of a disorder of the basal ganglia. In 1 patient with macrocephalus the disorder was diagnosed before the onset of neurological disease; in another it was diagnosed prenatally. Computed tomography and magnetic resonance imaging scans revealed severe generalized cerebral atrophy, most striking in the frontal and temporal lobes in 10 patients. Further deterioration was halted after initiation of treatment consisting of low-protein diets, special formulas low in lysine and tryptophan, and supplements of riboflavin and L-carnitine. Only 1 patient showed a slight clinical improvement. Later, dietary therapy was discontinued in 2 older patients and relaxed in a third without observed adverse effects. Two patients in whom treatment could be initiated before the onset of neurological symptoms have developed normally. However, duration of follow-up (6 and 29 months) does not yet allow classification of glutaryl-coenzyme A dehydrogenase deficiency as a treatable disorder. Total body production of glutaric acid, reflected in the daily urinary output, was efficiently reduced by therapeutic measures. Levels of glutaric acid in plasma and cerebrospinal fluid remained unchanged, which may in part explain the overall unsatisfactory outcome. All patients presented with a severe secondary deficiency of carnitine.(ABSTRACT TRUNCATED AT 250 WORDS)

Taurine metabolism in experimental renal failure.

Taurine is important for the regulation of ionic fluxes in excitable tissues, especially in heart where it is the most abundant amino acid. To investigate a possible role of taurine in uremia, we measured the taurine concentrations in plasma, liver, muscle, heart, and brain tissues of young male Wistar rats. Two groups of rats were studied: (1) rats with acute renal failure (ARF) 12, 24, and 48 hours after bilateral nephrectomy and (2) rats with chronic renal failure (CRF) studied 3 weeks after 5/6 nephrectomy. In ARF animals, taurine increased in plasma and liver two to three times the normal levels, remained unchanged in muscle and brain, but decreased in heart tissue; this decrease (-20%) was significantly correlated with the concomitant increase of BUN and plasma creatinine. In CRF animals, taurine was unchanged in plasma, liver, muscle, and heart, but was increased by 70% in brain accompanied by a high content of gamma-aminoisobutyric acid. The data suggest that in uremia accumulation of taurine is counteracted by increased hepatic elimination and/or decreased synthesis. The depletion of taurine in cardiac muscle might be related to the development of uremic heart disease. The increased concentrations of brain taurine might represent a compensation for the increased neuroexcitability in CRF.

Adenine nucleotide translocation in liver mitochondria isolated from rats deficient in essential fatty acids.

Adenine nucleotide content and adenine nucleotide transport were evaluated in rats deficient in essential fatty acids (EFA) and in control rats. ADP uptake by EFA-deficient mitochondria was altered in a manner similar to the alteration produced by treatment of normal mitochondria with uncoupler. The uptake of ATP by EFA-deficient mitochondria was more rapid than that of normal mitochondria, but similar to that of normal mitochondria treated with uncoupler (DNP). Both uptake of ADP and uptake of ATP by EFA-deficient mitochondria were atractyloside sensitive. Total adenine nucleotide content of liver mitochondria from EFA-deficient rats was similar to that of liver mitochondria from control animals, but the content of ATP in EFA-deficient mitochondria was significantly higher than that of normal mitochondria. There was a negative correlation between the concentration of linoleic acid in total mitochondria lipids and ATP content of mitochondria.

Stereodifferentiation of 3-hydroxyisobutyric- and 3-aminoisobutyric acid in human urine by enantioselective multidimensional capillary gas chromatography-mass spectrometry.

The chiral metabolites 3-hydroxyisobutyric acid (HIBA) and 3-aminoisobutyric acid (AIBA) are intermediates in the pathways of L-valine and thymine and play an important role in the diagnosis of the very rare inherited metabolic diseases 3-hydroxyisobutyric aciduria (McKusick 236975) and methylmalonic semialdehyde dehydrogenase deficiency (McKusick 603178-MSDD). Until now only a few approaches have been made in enantioselective analysis of HIBA and AIBA and for that reason very little information is available on enantiomeric ratios of these metabolites in man. This paper reports on the simultaneous stereodifferentiation of HIBA and AIBA in human urine as corresponding N(O)-methoxycarbonyl methyl esters by derivatization with methyl chloroformate (MCF) using enantioselective multidimensional gas chromatography-mass spectrometry (enantio-MDGC/MS) with heptakis-(2, 3-di-O-methyl-6-O-tert.-butyl-dimethylsilyl)-beta-cyclodextrin as the chiral stationary phase. During this investigation urine samples from different patients and healthy controls were analyzed in order to reveal characteristic enantiomeric patterns of these metabolites. A trend of dominating R-HIBA excretion in the control urine samples investigated was observed. An excretion of more than 80% S-HIBA was found in the urines of two patients with ketonemic vomiting. There are some clues indicating a possible renal reabsorbtion of S-HIBA similar to those of S-AIBA. Furthermore, there was a significant finding with regard to the enantiomeric distribution of AIBA in a patient with MSDD - a markedly increased excretion of the S-enantiomer in contrast to the other samples. Using the enantiomeric ratios of AIBA, a previously investigated case of benign methylmalonic aciduria (bMMA) could be excluded from the diagnosis of MSDD.

Tissue carnitine concentrations after total parenteral nutrition with and without L-carnitine supplementation.

The concentrations (mumoles/g dry weight) of total carnitine (TC), free carnitine (FC) and acylcarnitine (AC) were determined in skeletal muscle, heart, liver, kidney and brain cortex of male mini pigs (4000-5000 g) after seven days of total parenteral nutrition (TPN) with amino acids 5% (3.0g/kg/d), glucose (25g/kg/d) and lipids 20% (4g/kg/d). This regime was administered with L-carnitine supplementation (1.5 mg/kg/d; n = 7) (group 1) and without it (n = 5) (group 2). Orally alimented animals (n = 5) served as controls (group 3). (Average carnitine intake: 3 mg/d) Carnitine free TPN affected only the concentrations in muscle. TC was markedly reduced (3.6 +/- 0.8) when compared with oral controls (5.8 +/- 0.7) (p<0.01). This decrease was exclusively due to AC, whereas FC concentrations remained almost unchanged. In group 1 the concentrations of TC in skeletal muscle, heart and brain cortex were higher than in both the other groups. The increase was mainly due to AC and FC remained unchanged in heart and brain. The concentrations in liver and kidney were not affected by either carnitine free or carnitine supplemented TPN. AC, determined as described, consists almost entirely of acid soluble acetyl-carnitine, the major product of fatty acid oxidation. Since the AC concentrations were almost exclusively altered by the two TPN-regimes we conclude that the observed changes reflect regulatory changes of fatty acid oxidation. Thus the decrease of muscle TC in group 2 is considered a consequence of an insulin induced down regulation (plasma insulin: mean 20 muU/ml; maximum: 60 muU/ml) of fatty acid oxidation in consequence of high glucose intake (25 g/kg/d). The increased TC concentrations after carnitine supplemented TPN are discussed to reflect an enhancement of oxidative degradation of fatty acids as a pharmacological effect of L-carnitine.

Antioxidant vitamins in prevention.

The authors are aware that there is still a need for much research to elucidate the possible preventive effects of antioxidant vitamins with regard to degenerative and neoplastic diseases. There must also be vigorous examination of the evidence that antioxidant vitamins can play a crucial part in a large number of other disorders (Alzheimer's disease, Parkinson's disease, diabetes, chronic and acute inflammations, airway disorders, reperfusion syndrome). The aim of prevention-oriented medical research must be to develop suitable measures able to make a considerable contribution to the overall prevention policy. Although there is still uncertainty about the mode of action and the optimal dosage of antioxidant nutrients and dietary constituents, particularly because of the safety when the dosage is correct, more information must be provided about early prevention of an inappropriate, low antioxidant intake; intake in the diet should definitely be preferred to supplementation because of the other beneficial effects of the recommended foodstuffs.

High-dose intravenous vitamin C is not associated with an increase of pro-oxidative biomarkers.

OBJECTIVE: High-dose vitamin C therapy might mediate beneficial clinical effects by counteracting reactive oxygen species. However, concerns are raised whether this approach might provoke diametrical (ie pro-oxidative) effects. The objective was to determine ascorbyl free radical (AFR) concentrations and potential variables of pro-oxidative damage. DESIGN: Crossover study; six healthy males received daily infusions of 750 or 7500 mg vitamin C for six consecutive days. Fasting concentrations of vitamin C and AFR were determined daily. On day 1, concentrations of vitamin C and AFR were measured at 0.25, 0.5, 1, 2, 4 and 8 h post infusion. Plasma concentrations of thiobarbituric acid-reactive substances (TBARS), tocopherol and urine concentrations of 8-oxoguanosine were determined on days 1 and 6. RESULTS: Kinetic studies on day 1 showed that concentrations of vitamin C and AFR displayed parallel dose- and time-dependent kinetics and elimination was highly efficient. Vitamin C and AFR fasting concentrations on days 2-6 were slightly above the baseline, suggesting new, stable steady states. TBARS decreased in both groups, whereas tocopherol and 8-oxoguanosine concentrations remained unchanged. CONCLUSION: Kinetics of AFR largely depend on plasma vitamin C concentrations and AFR is eliminated efficiently. Our data do not support induction of pro-oxidative effects in healthy volunteers given intravenous high-dose vitamin C. SPONSORSHIP: Pascoe Pharmazeutische Präparate GmbH, Giessen, Germany.

The influence of intravenous medium- and long-chain triglycerides and carnitine on the excretion of dicarboxylic acids.

Four groups of male Wistar rats were alimented parenterally for 3 days. Groups 1 and 2 received medium-chain triglycerides (MCT) and groups 3 and 4 long-chain triglycerides (LCT). Groups 2 and 4 were supplemented with 100 mg L-carnitine/kg/day. The MCT-alimented rats presented with a distinct excretion of the dicarboxylic acids: adipic acid (C6), suberic acid (C8), and sebacic acid (C10). The acids excreted corresponded to the infused pattern of monocarboxylic acids: caproic acid (C6), caprylic acid (C8), and capric acid (C10). Dicarboxylic acid excretion after MCT administration may reflect an insufficient capacity of beta-oxidation on one hand or a preferential omega-oxidation of medium-chain fatty acids on the other. Carnitine supplementation lead to a further increase of the dicarboxylic acids in the MCT-group. beta-OH-butyric acid excretion decreased after carnitine in the MCT as well as in the LCT group. An increased transport of fatty acid-carnitine compounds out of the mitochondria is discussed as an important effect of carnitine supplementation. Hereby medium-chain fatty acids may be more accessible for omega-oxidation.

Improved N-retention during L-carnitine-supplemented total parenteral nutrition.

The influence of intravenously administered L-carnitine on lipid- and nitrogen-metabolism was studied during total parenteral nutrition of piglets (mean weight 4077 g; n = 9). The infusion protocol was divided into three isocaloric and isonitrogenous 48-hr periods. Amino acids (3 g/kg day) were administered throughout all three periods: 140 cal/kg/day were given as nonprotein calories, consisting only of glucose during period 1; during periods 2 and 3, an amount of glucose calorically equivalent to 4 g fat/kg/day was substituted with a lipid emulsion, and L-carnitine (1.5 mg/kg/day) was added in period 3. Key parameters of fat- and nitrogen-metabolism were determined during the entire regime. Indirect calorimetry was performed and the respiratory quotient calculated during all three periods. The results demonstrate a more effective lipolysis and oxidation of fatty acids during L-carnitine supplementation. These changes produce an increased energy gain from exogenously administered fat and a distinct improvement in nitrogen balance.

Ineffectiveness of oral coenzyme Q10 supplementation in 3-methylglutaconic aciduria, type 3.

Coenzyme Q10 was administered under placebo controlled blinded crossover conditions to six subjects suffering from type 3 3-methylglutaconic aciduria ('optic atrophy plus'), following a report of benefit. Despite attainment of high plasma levels of coenzyme Q10, no clinical benefit was observed and there was no diminution of urinary excretion of 3-methylglutaconic acid.

Serum carnitine levels, lipid profile, and metabolic status of patients on continuous ambulatory peritoneal dialysis.

The purpose of our study was to evaluate the influence of serum carnitine levels on the metabolic status and lipid profile of patients on continuous ambulatory peritoneal dialysis (CAPD). We studied the lipid profile, the metabolic status (triceps, skinfold thickness, midarm muscle circumference, relative body weight, serum total protein, albumin), and serum carnitine levels in 22 patients (11 male, 11 female) on CAPD. The results are summarized as follows: mean serum total carnitine (TC) was normal, free carnitine (FC) was reduced, while acylcarnitine (AC) was elevated in our patients (p < 0.001). A positive correlation was found between TC (p < 0.02), FC (p < 0.05), and serum total protein. A positive correlation was also found between TC (p < 0.05), AC (p < 0.02), AC/FC (p < 0.02), and relative body weight, and TC (p < 0.001), FC (p < 0.02), AC (p < 0.01), AC/FC (p < 0.02), and triglycerides. No correlation was found between carnitine and mid-arm muscle circumference, triceps skinfold thickness, albumin, total cholesterol, and HDL- or LDL-cholesterol. Further studies are needed to confirm our results.

Evaluation of carnitine levels according to the peritoneal equilibration test in patients on continuous ambulatory peritoneal dialysis.

The evidence of carnitine abnormal metabolism in patients on continuous ambulatory peritoneal dialysis (CAPD) is unclear, and previous studies have reported conflicting results. The total (TC), free (FC), and acylated (AC) carnitines were estimated in blood and dialysate, as well as the AC/FC ratio, in 29 patients on CAPD, grouped into high (H-Abs) and low (L-Abs) absorbers, according to the results of the peritoneal equilibration test (fast PE-test). Our data demonstrated that patients with higher peritoneal transport rates, which was the H-Abs group, males and females, showed a better carnitine metabolic status compared to the L-Abs group. Although the H-Abs group lost significantly more free carnitine than the L-Abs group, the AC/FC ratio of the H-Abs group remained within normal range. All the patients in our study showed abnormally high triglyceride (TRG) levels and an abnormally high total cholesterol/HDL cholesterol ratio. In particular, the patients in the L-Abs group showed significantly higher TRG levels and total cholesterol/HDL cholesterol ratios than the H-Abs group. Those patients who have been on CAPD for more than 2 years showed significantly abnormally higher AC/FC ratios than those with shorter periods on CAPD treatment. In patients with AC/FC ratio greater than 0.4, the supplementation of L-carnitine may have a beneficial effect on their carnitine and lipid metabolism.

Antioxidative vitamins in prematurely and maturely born infants.

Postnatally a rapid change occurs from a relatively hypoxic to a relatively hyperoxic environment, especially during artificial ventilation with all risks of ROS-formation. Among the non enzymatic antioxidative strategies the vitamins E, C, A and B2 are of major importance. Vitamin E is considered the most important radical scavenging vitamin of the lipid soluble compartment. Hereby vitamin E itself is converted into a radical which is handed over to vitamin C and glutathione into the water soluble compartment. The vitamin E content of the fetus increases with the fetal fat mass mainly during the last trimester of pregnancy. Placenta is only slightly permeable to lipid soluble vitamins. Vitamin E deficiency may rapidly develop typically at about 6-8 weeks of age. Vitamin E is able to prolong significantly the onset of retinopathic changes during oxygen therapy and may prevent intraventricular hemorrhage. Vitamin C is together with glutathione a major representative of the non enzymatic antioxidative system in the water soluble compartment. The best determinant of the vitamin C status is its concentration in leukocytes. Vitamin C reduces iron to the divalent state which supports the hydroxyl radical formation (Haber-Weiss reaction). This should be considered mainly in cases of intraventricular hemorrhage. Vitamin B2 acts mainly as cofactor of glutathione reductase which keeps glutathione in the reduced state. It can therefore be considered an indirect antioxidative vitamin. Vitamin B2 is destroyed by light. Phototherapy has been recognized as a cause of riboflavin deficiency. Vitamin A comprises all retinols with properties like trans-retinol. Retinol storage in the fetal liver increases during late pregnancy. In both, premature and mature newborns, the serum concentrations amount to only about 50% of those of their mothers. Vitamin A has a paramount importance for fetal lung development, because the individual surfactant proteins are selectively regulated by retinoic acid.