Subject niacin

Treatment of tardive dyskinesia is often unsatisfactory, especially in severe cases. A large number of treatments have been proposed (SEDA-20,40), including antiparkinsonian drugs, benzodiazepines, baclofen, hormones, calcium channel blockers, valproate, propranolol, opiates, cyproheptadine, tryptophan, lithium, manganese, niacin, botulinum toxin, ECT, dietary control, and biofeedback training. In an open study, 20 patients (mean age 65 years) with severe unresponsive tardive dyskinesia (mean duration 44 months, mean exposure 52 months) were treated with tetrabenazine (mean dose 58 mg/day) (310). The mean score on the AIMS motor subset, determined from videotapes, improved by 54%. Sedation was the only subjective complaint. 

A number of studies have investigated the equivalence of dietary tryptophan and preformed niacin as precursors of the nicotinamide nucleotides, generally by determining the excretion of -methyl nicotinamide and methyl pyridone carboxamide in response to test doses of the precursors, in subjects maintained on deficient diets. 

The most extensive such study was that of Horwitt and coworkers (1956). They found that there was a considerable variation between subjects in the response to tryptophan and niacin, and suggested that in order to allow for individual variation, it should be assumed that 60 mg of tryptophan was equivalent to 1 mg of preformed niacin. This ratio has been generally accepted, and is the basis for expressing niacin requirements and intake in terms of niacin equivalents - the sum of preformed niacin and 1 /60 of the tryptophan. 

Erythrocyte NAD falls during niacin depletion and rises during repletion in human subjects. Erythrocyte NADP is unaffected, and the ratio of NADiNADP provides a useful index of niacin nutritional stams, with a ratio <1.0 indicating deficiency (Fu et al., 1989). 

The depletion/repletion studies of Horwitt et al. (1956) and others have suggested, on the basis of restoration of urinary excretion of -methyl nicotinamide, that the average niacin requirement is 5.5 mg per 1,000 kcal (1.3 mg per MJ). Allowing for individual variation, reference intakes (see Table 8.2) are set at 6.6 mg niacin equivalents (preformed niacin - -1 /60 of the dietary tryptophan) per 1,000 kcal (1.6 mgper MJ). Even when energy intakes are very low, it must be assumed that energy expenditure will not fall below 2,000 kcal, and this is the basis for the calculation of reference intakes for subjects with low energy intakes. 

The excretion of methyl pyridone carboxamide is more severely reduced in marginal niacin deficiency than is that of -methyl nicotinamide. The excretion of methyl pyridone carboxamide decreases rapidly in subjects fed on a niacin-deficient diet, and virtually ceases several weeks before the appearance of clinical signs of deficiency by contrast, a number of studies have shown continuing excretion of -methyl nicotinamide even in pellagrins. A better estimate of niacin nutritional status can be obtained by determining the ratio of urinary methyl pyridone carboxamide Ai -methyl nicotinamide, which is relatively constant, despite the administration of loading doses of tryptophan or niacin to adequately nourished subjects (between 1.3 to 4.0), and a ratio of less than 1.0 indicates depletion of niacin reserves (de Eange and Joubert, 1964 Dillon et al., 1992). 

It is generally accepted that under normal conditions human subjects convert the largest part of an ingested dose of L-tryptophan to non-aromatic products. The last identified benzene derivative on this pathway is 3-hydroxyanthranilic acid when its ring is opened to form unstable intermediates, apparently only a small percentage of them are converted to niacin (H8). 

Auricchio et al. (A12) analyzed the excretory pattern of 6 children with leukemia and 2 with Hodgkin s disease. No definite relationship could be observed between the disease and the abnormally elevated amounts of tryptophan metabolites. After niacin therapy the urinary excretion of kynurenines and kynurenic and xanthurenic acids was normalized in one case of Hodgkin s disease and in one leukemic subject after pyridoxine administration. 

Use of nicotinic acid (niacin, B3) to abort psychosis - We have given the subject 100 ug. of LSD at the height of the experience we injected intravenously 200 mg. of nicotinic acid. Our experience has been that, within a matter of two to five minutes, almost all of the LSD phenomena disappeared, and the subject claimed that he was entirely normal, Abraham Hoffer (1956)... 

A detailed molecular characterization of the human NAPRT was reported only recently, and it was shown that the activity of this enzyme (in contrast to NMPRT) is not a subject of feedback inhibition by the physiological levels of NAD. This finding may provide a rationale for the observation that the increased levels of Na, but not Nm, in circulation leads to the increase in the NAD cellular pool, emphasizing the different roles of these two forms of niacin in nutrition and signaling in mammals (for a review, see Bogan and Brenner ). 

V2. Vivian, V. M., Chaloupka, M. M., and Reynolds, M. S., Some aspects of tryptophan metabolism in human subjects. I. Nitrogen balances, blood pyridine nucleotides and urinary excretion of N-methyliiicotinamide and N-methyl-2-pyridone-5-carboxamide on a low-niacin diet. J. Nutr, 66, 587-598 (1958). 

Watson and Yudkin (1959) investigated the urinary excretion of thiamine, riboflavin, and niacin (as JV-methylniacinamide) in one subject... 

The analysis for niacinamide for all County subjects was done by the microbiological method described by Strohecker and Henning (1966) with use of a strain of Lactobacillus arabinosus (ATCC 8014) responding to niacin, niacinamide, and nicotinuric acid. The procedure was very time-consuming, and was discarded after the development of the chromatographic method described below. The measured amounts were converted by an empirical factor to correspond to the results of the chromatographic method. 

The protective effect of niacin against cardiovascular disease is subject of ongoing clinical trials. 

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