High levels of dietary arachidonic acid triglyceride exhibit no subchronic toxicity in rats.

Arachidonic acid (AA), an n-6 long-chain polyunsaturated fatty acid (LC-PUFA), serves an important role in the body as a structural fatty acid of many tissues including neurological tissues. It is also a precursor of the n-6 class of eicosanoids and is the most abundant n-6 LC-PUFA found in human breast milk. We have optimized the production of a microfungal source of a triglyceride oil (ARASCO) which is enriched in AA to about 40% by weight. To establish the safety of this oil as a food, we evaluated the effect of ARASCO in Sprague-Dawley rats (20/sex/group) gavaged at dose levels of 1.0 and 2.5 g/kg/d for a period of 90 d, paying special attention to any potential neurotoxicity of the oil. Two groups of control animals received either untreated standard laboratory diet (untreated control) or the same diet and vehicle oil at the same dose volume administered to the treated animals (vehicle control). Physical observations, ophthalmoscopic examinations, body weight, food consumption, clinical chemistry, hematology parameters, neurobehavioral assessments, and macroscopic as well as microscopic postmortem evaluations were performed. Tissue fatty acid analyses indicated that the AA levels in the brain, heart, and liver of the high-dose ARASCO-fed animals increased by 8, 59, and 76%, respectively, indicating that the AA in the oil was readily incorporated into tissue lipids. In spite of this high elevation in tissue AA levels, no developmental, histopathological, or neuropathological differences were seen in the animals administered ARASCO compared with the vehicle control animals. Being highly enriched in AA, ARASCO offers the means to study the effect of this fatty acid in experimental settings and in human metabolic studies.

Preclinical evaluation of single-cell oils that are highly enriched with arachidonic acid and docosahexaenoic acid.

Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important in human brain and retina development, and there is growing evidence showing the importance of these fatty acids in infant nutrition. Triglyceride oils, highly enriched in ARA (ARASCO) and DHA (DHASCO), were evaluated using very high dose acute (20 g/kg) and 4-wk subchronic gavage feedings in weanling Sprague-Dawley rats. The combination of these oils, Formulaid, was also tested in the 4-wk subchronic study, ARASCO, DHASCO and Formulaid were found to have a no-observable-adverse-effect level of more than 2.5 g/ kg/day, 1.25 g/kg/day and 3.75 g/kg/day, respectively. This represents a 50-fold safety margin over the intended use of Formulaid in infant formula. Survival, clinical signs, body weight gain, food consumption, haematology, clinical chemistry and histopathological evaluations failed to show any significant differences in animals administered ARASCO, DHASCO or Formulaid compared with that in control animals administered equal amounts of high oleic sunflower oil. The bioavailability of ARASCO, DHASCO and Formulaid was verified by increases in DHA and ARA levels in heart and liver tissues in these animals. Because these oils are enriched in only a single bioactive fatty acid, and they have been shown to be safe, they may offer a new source of these fatty acids in speciality foods such as infant formula.

Quantitation of muscles and fat by ultrasonography: a useful method in the assessment of malnutrition in children.

We used ultrasonography to measure muscles in the arms and thighs of 16 children with malignant diseases. Thicknesses of transverse sections of the brachial biceps muscle and the femoral quadriceps muscle were measured by ultrasound at the midpoint of the right arm and thigh. These two measures had a linear correlation (r = 0.76). The ultrasound measurements did not differ from those obtained by the CT scan which was used as a reference standard. The reproducibility of the measurements was good; the coefficient of variation was 2.4% for the midarm muscles and 2.8% for the midthigh muscles. We conclude that the ultrasound method combined with simple anthropometric measurements is helpful in the assessment of nutritional status of children with potential malnutrition.

Serum tumor necrosis factor does not correlate with changes in muscle volume in children with malignancies.

This study examined the connection between serum tumor necrosis factor (TNF) concentration and the development of cachexia in 12 children with acute lymphoblastic leukemia (ALL). The changes in muscle thickness were used as criteria for malnutrition, estimated by an ultrasound method during the 16 weeks of chemotherapy subsequent to diagnosis. Serum TNF concentrations were elevated at diagnosis and gradually decreased toward the reference limits by week 16. There was no correlation between TNF and muscle thickness. The results were also compared to those obtained from 8 children with other malignancies in whom the mean relative weight remained below normal whereas in those with ALL it gradually increased to +15%. Thus, we found no evidence of the association between elevated serum TNF concentrations and cachexia in man.

Low levels of serum transport proteins indicate catabolic protein status during induction therapy for acute lymphoblastic leukemia.

Twelve children with newly diagnosed acute lymphoblastic leukemia (ALL) were followed during the first 24 weeks of induction and consolidation therapy. Twelve additional patients with other types of cancer, receiving no prednisone medication, served as a reference group. The serum total protein, albumin, transferrin, and prealbumin concentrations were measured at 0, 2, 4, 6-10, 16, and 24 weeks and used as biochemical indices of protein nutritional status. In all patients studied, serum albumin and prealbumin concentrations were low at diagnosis. Decreasing serum total protein and transferrin concentrations, stable low serum albumin, and increasing prealbumin levels were observed during the ALL induction therapy. In contrast, these protein levels remained stable in the children with other malignancies. By week 8 the patients with ALL had lower serum total protein, albumin, and transferrin than the children with other types of cancer. We conclude that the low levels of the serum transport proteins indicate catabolic protein status in children with ALL during early weeks of therapy.

Serum selenium in children during anti-cancer chemotherapy.

Serum selenium concentration as an indicator of selenium status was studied during a 6-month period in 24 children with acute leukaemia or solid tumours. At diagnosis low serum selenium values were found in children with acute leukaemia compared to children with solid tumours (P = 0.001), while there were no differences in the protein nutritional status of these children as assessed by serum albumin and prealbumin. During the corticosteroid treatment serum selenium levels increased (mean of 111 per cent) in children with acute leukaemia. The concentrations of serum selenium remained within the reference range of healthy Finnish children from week 16 onwards in children with acute leukaemia and throughout the study period of 24 weeks in children with solid tumours. The results suggest redistribution of the endogenous selenium stores since no selenium supplementation was used, and demonstrate that serum selenium is not a valid indicator of selenium status in these cases.

Skeletal muscle wasting and protein-energy malnutrition in children with a newly diagnosed acute leukemia.

The changes in skeletal muscle mass of 14 children with newly diagnosed acute leukemia were studied during the first 24 weeks of antileukemia therapy. A muscle index was calculated from the femoral quadriceps muscle thickness, measured by using an ultrasound method, and from the body surface area. Serum albumin concentration was used as a biochemical indicator of protein status. Some children had muscle wasting before diagnosis. The highest degree of muscle wasting developed by 4 to 6 weeks with an average of 27% decrease of the muscle index. Because of simultaneous increase of adipose tissue (average, 33% at 6 weeks and 37% at 12 weeks), the relative body weight or the limb circumferences did not decrease. Muscle mass recovery occurred within the next 6 months. Our data emphasize that changes in the relative body weight or limb circumferences do not reveal nutritional protein depletion and muscle wasting that occurs in children with newly diagnosed acute leukemia.

Tumor necrosis factor in children with malignancies.

We measured serum tumor necrosis factor alpha (TNF) concentrations by a double-antibody radioimmunoassay method, with a detection level of 10 ng/liter, in 32 children with malignancies. Seventeen had acute lymphoblastic leukemia, 4 had acute nonlymphocytic leukemia, and 11 had solid tumors. At the diagnosis of malignant disease, 30 of the 32 patients had elevated serum TNF levels ranging up to 450 ng/liter. After complete remission status was achieved, 2-6 months from the diagnosis, the TNF levels were within the range of 130 healthy children who served as the reference group. Most of them had TNF levels below the detection limit. We consider the upper limit of normal to be 40 ng/liter. We conclude that elevated serum TNF concentration may be of potential significance in the diagnosis and follow-up of children with malignant diseases.