Effect of an excess intake of leucine, with and without additions of vitamin B6 and/or niacin, on tryptophan and niacin metabolism in rats.
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Lots of growing or adult rats consume ad libitum diets based on zein (12 p. 100 of protein) (diets A), or on zein partially supplemented by lysine and tryptophan (= protein quality of maize) (diets B), or on zein supplemented by amino acids to fill its deficiencies totally (diets C). The diets contain 15 mg of niacine per kg. The diets A 1, B 1 and C 1 receive an addition of 10 mg of supplementary niacin. The efficiency is estimated by the amount of niacin and tryptophan in blood plasma and in liver. The niacin efficiency depends more on the protein quality - more precisely of the intake of tryptophan - than the intake of niacin: the hepatic concentrations of niacin are 120 mug with diet A and 210 mug with diet C in growing rats. These variations are identical to the evolution of intakes and of concentrations of liver nitrogen. The administration of a supplement of niacin (10 mg/kg) does not cause repercussion on the body niacine on the growing rat and provokes a very weak profit on the adult animal. In the dietsA (unsupplemented zein), only the tryptophan is an efficacious source of niacin. The niacin seems unable to increase the vitamin storage in the liver.
The effects of dietary deficiency and excess of niacin and riboflavin on voluntary drinking of 10% (v/v) ethanol were studied in male rats. The effectiveness of dietary deficiency and excess of both niacin and riboflavin on tissue levels of these vitamins was demonstrated by measurements of urinary N1-methylnicotinamide and blood glutathione reductase (EC 1.6.4.2) activity. A high-niacin diet containing 75 mg niacin/kg food decreased ethanol intake by about 36% compared to the control diet containing 15 mgniacin/kg. Niacin or riboflavin deficiency and a high-riboflavin diet containing 40 mg rtary levels of niacin or riboflavin did not influence on ethanol elimination rate or levels of blood acetaldehyde during ethanol oxidation. Therefore, blood acetaldehyde was not responsible for the decreased ethanol intake of rats fed with a high-niacin diet. It was concluded that the increased ethanol intake caused by dietary deprivation of B-vitamin complex found in earlier studies is not a result of deficiency of niacin or riboflavin but niacin may be involved in the decrease in ethanol drinking, which follows dietary B-vitamin complex supplementation.
A double-blind multiclinic trial compared the efficacies of pyridinolcarbamate and inositol niacinate in the patients with the ischemic ulcer due to chronic arterial occlusion. A thrice-daily dose of 1.5 g of pyridinolcarbamate or 1.2 g of inositol niacinate was given at random to the patients during cold seasons, and the effectiveness of treatment was assessed mainly on the basis of the clinical course of the ischemic ulcer and the rest pain. The patients were classified into 4- and 6-week groups. Beneficial results were recorded in 16 of 32 cases (50.0%) of the 4-week pyridinolcarbamate group, and in 24 of 42 cases (57.1%) of the 4-week inositol niacinate group. In the 6-week group favorable results were observed in 54 of 79 cases (68.4%) on pyridinolcarbamate, and in 36 of 74 cases (48.6%) on inositol niacinate. Although sympathectomy is currently indicated for these ischemic lesions, long-term treatment with pyridinolcarbamate is recommended on the basis of the finding that the 6-week treatment appears superior to the 4-week treatment and also to the 6-week treatment with inositiol niacinate.
Subjective discomfort caused by nausea and hot, pruritic skin has been described in patients after ingestion of therapeutic dosages of niacin is shown by this study to be alleviated by propranolol HC1. A dosage of 2 mg, I.V., given incrementally, in a clinical trial of six patients is described. The peripheral vasodilator effects of niacin were attenuated in some subjects but not in others. However, all subjects reported relief of unpleasant symptoms. Serial vital signs were taken and no significant changes were found. It is postulated that propranolol HC1 exerts a calmative effect at the CNS level. In a series that utilized doses of 40 and 80 mg of propranolol HC1 taken orally 30 min prior to the ingestion of 500 or 1000 mg of niacin, a progressive increase in the onset of the niacin flush was observed. It is proposed that as the available plasma level of propranolol HC1 falls, the ratio of niacin to propranolol HC1 increases, exceeding the threshold at which the flush occurs. Both these studies suggest that further work is indicated to establish the possible therapeutic efficacy of propranolol HC1.
The addition of a vitamin to a diet of humans has been shown to increase the excretion of that vitamin. The effects of an increase of one vitamin on another have not been investigated. The objective of the current project was to compare the effects of two supplementation patterns on the niacin and pantothenic acid excretion values of humans consuming a peanut butter-based diet. Two groups each received one of two supplementation regimens. One group received niacin, a multi-vitamin, or no supplement. One group received methionine alone, pantothenic acid alone or methionine plus pantothenic acid. The addition of either vitamin resulted in increased excretion of that vitamin. Urinary niacin excretion of the group that received pantothenic acid and/or methionine was greater than that observed with a multi-vitamin or no supplement. Urinary pantothenic acid excretion was suppressed when niacin was a supplement. Urinary pantothenic acid excretion of the methionine supplement group was greater than the excretion of the groups which received either niacin or multi-vitamin supplements. These data suggest some possible dangers in indiscriminate supplementation of food products.
Baby chicks were fed purified diets containing 90 g/kg casein and 100 g/kg gelatin. With low levels of niacin and tryptophan, niacin deficiency resulted: this was not exacerbated by the addition of supplementary leucine (17.4 g/kg). With levels of niacin and tryptophan that supported rapid growth the further addition of supplementary leucine depressed food consumption and weight gain; in most instances this was statistically significant. No evidence was obtained to indicate that a high level of dietary leucine could result in niacin deficiency in chicks. Comparable experiments were carried out with weanling rats given a basal diet containing 60 g/kg casein and 60 g/kg gelatin. Adding 15 g/kg L-leucine gave results similar to those obtained with chicks and the same conclusions were drawn.
By using the GI tube technique, niacin was shown to be equally well absorbed from the stomach and the upper small intestine. The maximum plasma niacin concentrations occurred 10-20 and 5-10 min, respectively, after instillation. Thus, the physiological prerequisites for a physically retarded niacin preparation were established.
Two feeding trials were designed to precipitate niacin deficiency in puppies receiving low levels of niacin by adding 15 g/kg supplementary l-leucine to a diet containing 180 g/kg casein. We failed to produce such an effect and, as niacin levels were gradually reduced, the times at which control dogs became deficient (and then responded to injections of the vitamin) were not significantly different from those for dogs receiving the leucine supplement. Differences between the conditions of our experiments and of the experiment in which this effect was found are discussed. Two pairs of littermates in trial 2 died suddenly while apparently in fairly good condition, but revealing fatty livers and/or changes in heart muscle on autopsy. Similar observations have been reported by others using purified diets with dogs over long periods; there is no certain explanation.
Channel catfish fingerlings were fed purified diets containing five levels (0, 25, 50, 100, and 150 mg/kg) and six levels (0, 5, 10, 25, 50, and 100 mg/kg) of supplemental niacin in 20 and 12 weeks feeding studies, respectively. The dietary niacin level required to provide maximal growth in rapidly growing channel catfish fingerlings was found to be approximately 14 mg/kg of diet. Fish fed unsupplemented diets (niacin content of 1.6 mg/kg diet) demonstrated poor growth, anemia, skin and fin lesions and hemorrhages, exophthalmia and total mortality in 20 weeks. Mortality and gross deficiency signs were prevented by 11.6 mg niacin/kg diet and anemia was prevented by 6.6 mg/kg. No histological abnormalities were observed in the heart, hepatopancreas, kidney, lateral muscle, gastrointestinal tract and gill tissues of deficient fish.
A radiometric microbiologic assay has been developed for the determination of niacin in biologic fluids. Lactobacillus plantarum produced 14CO2 from L-[U-14C] hr malic acid in quantities proportional to the amount of niacin present. The assay is specific for the biologically active forms of niacin in humans. Thirty normal hemolysates were analyzed and the values ranged from 13.0 to 17.8 micrograms niacin/ml RBC (mean = 15.27 +/- 1.33 s.d.). Good recovery and reproducibility studies were obtained with this assay. On thirty blood samples, correlation was excellent between the radiometric and the conventional turbidimetric assays.
In 227 students of the Institute for Physical Culture examined in the winter-spring and summer-fall seasons of the year, the passage of N1-methylnicotinamide (MNA) with urine per hour on an empty stomach amounted to 245 +/- 15.9 and 311 +/- 14.6 microgram/hour (the difference according to seasons in significant). These figues point to the dependence of the MNA excretion with uridine on the quantity of the niacin equivalents supplied together with the food. The content of such equivalentsin the rations of students-sprotrsmen (7-9.5 mg per 1000 calories per day) proved insufficient to maintain the MNA passage with urine at a level accepted as a standard allowance of niacin for the organism, i. e. 400-500 microgram/hour. Furthermore, the author shows changes in the niacin allowances of the student's organism, engaged in different kinds of sporting activities and also depending upon the sporting qualification of the examinees the work performed by them, the periods of training, and conditions of their every-day life.
1. Benserazide and carbidopa, decarboxylase inhibitors used in the treatment of Parkinson's disease, have been shown to inhibit the enzyme kynurenine hydrolase in rat and mouse liver. This results in reduced synthesis of nicotinamide coenzymes from tryptophan, and hence an increased reliance on dietary niacin. 2. Pellagra might be expected as a result of this inhibition of endogenous synthesis of nicotinamide nucleotides, but has not been reported in patients treated with either drug. 3. The urinary excretion of N1-methyl-nicotinamide, a product of nicotinamide nucleotide metabolism, is considerably reduced in patients treated with dopa alone or in combination with an inhibitor of peripheral dopa decarboxylase, to as low as 40% of the control value. This means that many of these patients could be classified as 'at risk' of niacin deficiency, even if not frankly deficient. 4. Patients treated with dopa plus a decarboxylase inhibitor, but not those treated with dopa alone, also show a reduced excretion of xanthurenic acid, and an increased excretion of kynurenine, as would be expected after inhibition of the kynurenine pathway, and possibly indicative of marginal vitamin B6 deficiency.
Biosynthesis of niacin from 3-hydroxyanthranilic acid (3-OHAA) in normal and streptozotocin diabetic rats was studied in vivo and in vitro. Streptozotocin (SZ) diabetic rats were found to excrete lesser quantities of 3-OHAA, quinolinic acid, niacin and N1-methylnicotinamide (nmn) in their urines following 3-OHAA administration than corresponding normal rats. In vitro studies indicated that SZ diabetic livers form less quinolinic acid from 3-OHAA than normal livers. It appears that this may be due to elevated picolinic carboxylase activity in the livers of SZ diabetic rats.
Young chicks were fed diets deficient in proteins, iron, niacin or thiamin to study the effects on various parameters of mineral metabolism in the duodenal mucosa. None of the treatments affected mucosal alkaline phosphatase activity; however, a five-day deprivation of protein reduced the inorganic phosphate content of mucosal cell nuclei. Iron deficiency reduced mucosal Ca, Zn, Fe and phosphate content, while niacin deficiency decreased mucosal Ca and phosphate. Thiamin deficiency reduced only the phosphate centent of intestinal mucosa. Duodenal phosphatase activity was positively correlated with tissue Ca and Fe and negatively with Zn.
Preparation and application of reagent impregnated paper strips for the detection of niacin are described. 170 cultures of mycobacteria were tested with the paper strips and by the conventional aniline-cyanogen bromide method. The results obtained demonstrate a high degree of correlation. Because of its advantages in comparison to the aniline-cyanogen bromide method-the toxic cyanogen bromide is omitted; malachite green does not disturb the reaction-the paper strip test can be recommended without reservation for the detection of niacin in microbiological laboratories.
A high-pressure liquid chromatographic procedure for the simultaneous determination of niacin and niacinamide in multivitamin preparations was developed and evaluated. Reversed-phase liquid chromatography with dioctyl sodium sulfosuccinate in the mobile phase is utilized for the analysis. The accuracy and precision of the procedure were compared with those of the currently official procedure.
A high-pressure liquid chromatographic procedure for the simultaneous determination of niacin, niacinamide, pyridoxine, thiamine, and riboflavin was developed and applied to the analysis of multivitamin blends for these water-soluble vitamins. Reversed-phase ion-pair chromatography, using sodium hexanesulfonate as the counterion, was employed. Analysis time is shortened considerably and precision is improved by the application of this analytical technique as compared to the current official methods of analysis. Involved sample pretreatment is not required.